Comparison of neutrophil and capillary diameters and their relation to neutrophil sequestration in the lung

1993 ◽  
Vol 74 (6) ◽  
pp. 3040-3045 ◽  
Author(s):  
C. M. Doerschuk ◽  
N. Beyers ◽  
H. O. Coxson ◽  
B. Wiggs ◽  
J. C. Hogg
Keyword(s):  
Pulmonary Circulation ◽  
Blood Cells ◽  
Polymorphonuclear Leukocytes ◽  
Neutrophil Sequestration ◽  
Pulmonary Capillaries ◽  
Pulmonary Capillary ◽  
Capillary Bed ◽  
The Mean ◽  
Pass Through ◽  
Capillary Size

Neutrophils [polymorphonuclear leukocytes (PMNs)] are sequestrated in the lung capillary bed because PMNs are delayed with respect to red blood cells (RBCs) as they pass through these microvessels. The present study examines circulating PMN size in relation to the distribution of capillary segment diameters in human, dog, and rabbit lungs and compares the shape of PMNs in suspension to that found within the pulmonary capillaries. The data show that 61, 67, and 38% of the capillary segments are narrower than the mean diameter of spherical PMNs in the rabbit, dog, and human, respectively. They also show that PMNs deform from a spherical to an ellipsoid shape in the pulmonary capillaries of all three species. These findings are consistent with previous studies showing that the pulmonary circulation restricts the passage of PMNs through the lungs and suggest that PMNs are delayed because they must deform to pass through restrictions encountered in the pulmonary capillary bed. We conclude that the discrepancy between PMN and pulmonary capillary size and the decreased deformability of PMNs with respect to RBCs are major determinants of the delay that PMNs experience with respect to RBCs in the pulmonary circulation.

scholarly journals Effect of mechanical deformation on structure and function of polymorphonuclear leukocytes

1997 ◽  
Vol 82 (5) ◽  
pp. 1397-1405 ◽  
Author(s):  
Yuko Kitagawa ◽  
Stephan F. Van Eeden ◽  
Darlene M. Redenbach ◽  
Maleki Daya ◽  
Blair A. M. Walker ◽  
...  
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Polarization Characteristic ◽  
Mechanical Deformation ◽  
Structure And Function ◽  
Functional Changes ◽  
Flow Cytometric ◽  
Pulmonary Capillaries ◽  
Pulmonary Capillary ◽  
Capillary Bed ◽  
And Function

Kitagawa, Yuko, Stephan F. Van Eeden, Darlene M. Redenbach, Maleki Daya, Blair A. M. Walker, Maria E. Klut, Barry R. Wiggs, and James C. Hogg. Effect of mechanical deformation on structure and function of polymorphonuclear leukocytes. J. Appl. Physiol. 82(5): 1397–1405, 1997.—The present studies were designed to test the hypothesis that mechanical deformation of polymorphonuclear leukocytes (PMN) leads to functional changes that might influence their transit in the pulmonary capillaries. Human leukocytes were passed through 5- or 3-μm-pore polycarbonate filters under controlled conditions. Morphometric analysis showed that the majority of PMN were deformed and that this deformation persisted longer after filtration through 3-μm filters than through 5-μm filters ( P < 0.05) but did not result in the cytoskeletal polarization characteristic of migrating cells. Flow cytometric studies of the filtered PMN showed that there was a transient increase in the cytosolic free Ca2+ concentration after both 3- and 5-μm filtration ( P< 0.01) with an increase in F-actin content after 3-μm filtration ( P < 0.05). AlthoughL-selectin expression on PMN was not changed by either 5- or 3-μm filtration, CD18 and CD11b were increased by 3-μm filtration ( P < 0.05). Priming of the PMN with N-formyl-methionyl-leucyl-phenylalanine (0.5 nM) before filtration resulted in an increase of CD11b by both 5 ( P < 0.05)- and 3-μm ( P < 0.01) filtration. Neither 5- nor 3-μm filtration induced hydrogen peroxide production. We conclude that mechanical deformation of PMN, similar to what occurs in the pulmonary microvessels, induces both structural and functional changes in the cells, which might influence their passage through the pulmonary capillary bed.

Computer simulation of neutrophil transit through the pulmonary capillary bed

1993 ◽  
Vol 74 (4) ◽  
pp. 1647-1652 ◽  
Author(s):  
C. C. Hanger ◽  
W. W. Wagner ◽  
S. J. Janke ◽  
T. C. Lloyd ◽  
R. L. Capen
Keyword(s):  
Computer Simulation ◽  
Computer Model ◽  
Pulmonary Circulation ◽  
Cell Deformation ◽  
In Vivo Microscopy ◽  
Pulmonary Capillaries ◽  
Pulmonary Capillary ◽  
Capillary Bed ◽  
Diameter Distributions

One-half of the neutrophils that enter the pulmonary circulation become temporarily trapped in capillaries. The neutrophils that are impeded make complete stops between free-flowing movements. These observations, based on in vivo microscopy, suggest that pulmonary margination is caused by neutrophils being impeded at focal sites in the capillary bed. To investigate the frequency with which impeding sites had to occur in the pulmonary capillaries to trap one-half of the circulating neutrophils, we developed a computer model to simulate neutrophils encountering discrete obstructions in a capillary-like network. Surprisingly, if only 1% of the capillaries in the network acted as traps, one-half of the neutrophils stopped at least once. The trapping ability of a given percentage of obstructions was independent both of the geometry of the network was whether the obstructions occurred in the segments or junctions. To simulate neutrophil transit more realistically, both neutrophil and capillary diameters were randomly selected from published diameter distributions. Every neutrophil was trapped multiple times by this model, suggesting that cell deformation contributes importantly to neutrophil passage through the pulmonary capillary bed.

Distribution of pulmonary capillary red blood cell transit times

1995 ◽  
Vol 79 (2) ◽  
pp. 382-388 ◽  
Author(s):  
R. G. Presson ◽  
J. A. Graham ◽  
C. C. Hanger ◽  
P. S. Godbey ◽  
S. A. Gebb ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Transit Time ◽  
Blood Cells ◽  
Time Distribution ◽  
Capillary Networks ◽  
Transit Times ◽  
Pulmonary Capillary ◽  
Capillary Bed ◽  
Transit Time Distribution ◽  
Pass Through

In theory, red blood cells can pass through the pulmonary capillaries too rapidly to be completely saturated with oxygen during exercise. This idea has not been directly tested because the transit times of the fastest red blood cells are unknown. We report the first measurements of the entire transit time distribution for red blood cells crossing single subpleural capillary networks of canine lung using in vivo fluorescence videomicroscopy and compare those times with the distribution of plasma transit times in the same capillary networks. On average, plasma took 1.4 times longer than red blood cells to pass through the capillary bed. Decreased transit times with increased cardiac output were mitigated by both capillary recruitment and a narrowing of the transit time distribution. This design feature of the pulmonary capillary bed kept the shortest times from falling below the theoretical minimum time for complete oxygenation.

Contributions of capillary pathway size and neutrophil deformability to neutrophil transit through rabbit lungs

1994 ◽  
Vol 77 (1) ◽  
pp. 463-470 ◽  
Author(s):  
B. R. Wiggs ◽  
D. English ◽  
W. M. Quinlan ◽  
N. A. Doyle ◽  
J. C. Hogg ◽  
...  
Keyword(s):  
Pulmonary Circulation ◽  
Blood Cells ◽  
Random Distribution ◽  
Large Fraction ◽  
Pulmonary Capillaries ◽  
Transit Times ◽  
Pulmonary Capillary ◽  
Time Required ◽  
Rapid Deformation

Neutrophil margination within the pulmonary capillary is due to a delay in their transit compared with that of red blood cells (RBC). This delay has been attributed to the large fraction of capillary segments that are narrower than spherical neutrophils and differences between the time required for deformation of neutrophils and that required for deformation of RBC. This study investigated the characteristics of neutrophil deformation in vivo and the perfusion patterns of segments within capillary pathways. Studies comparing the extraction of neutrophils with that of nondeformable microspheres in one transit through the pulmonary circulation suggest that neutrophils can undergo a rapid deformation from 6.4 to 5.0–5.1 microns, whereas larger deformations require a delay. Effective diameters of the perfused capillary pathways were larger than expected for a random distribution of capillary segment diameters within these pathways. The longer transit times of neutrophils in the upper regions of the lung were associated with a greater fraction of pathways containing narrow segments. These studies suggest that neutrophil deformability and capillary pathway diameters are important in determining the size of the marginated pool of neutrophils within the pulmonary capillaries.

Pulmonary capillaries are recruited during pulsatile flow

2002 ◽  
Vol 92 (3) ◽  
pp. 1183-1190 ◽  
Author(s):  
Robert G. Presson ◽  
William A. Baumgartner ◽  
Amanda J. Peterson ◽  
Robb W. Glenny ◽  
Wiltz W. Wagner
Keyword(s):  
Pulsatile Flow ◽  
Left Atrial ◽  
Pulmonary Arterial Pressure ◽  
Pressure Rise ◽  
Capillary Recruitment ◽  
Pulmonary Capillaries ◽  
Pulmonary Capillary ◽  
Direct Measurements ◽  
Pulmonary Arterial ◽  
The Mean

Capillaries recruit when pulmonary arterial pressure rises. The duration of increased pressure imposed in such experiments is usually on the order of minutes, although recent work shows that the recruitment response can occur in <4 s. In the present study, we investigate whether the brief pressure rise during cardiac systole can also cause recruitment and whether the recruitment is maintained during diastole. To study these basic aspects of pulmonary capillary hemodynamics, isolated dog lungs were pump perfused alternately by steady flow and pulsatile flow with the mean arterial and left atrial pressures held constant. Several direct measurements of capillary recruitment were made with videomicroscopy. The total number and total length of perfused capillaries increased significantly during pulsatile flow by 94 and 105%, respectively. Of the newly recruited capillaries, 92% were perfused by red blood cells throughout the pulsatile cycle. These data provide the first direct account of how the pulmonary capillaries respond to pulsatile flow by showing that capillaries are recruited during the systolic pulse and that, once open, the capillaries remain open throughout the pulsatile cycle.

Blood flow switching among pulmonary capillaries is decreased during high hematocrit

2004 ◽  
Vol 97 (2) ◽  
pp. 522-526 ◽  
Author(s):  
William A. Baumgartner ◽  
Amanda J. Peterson ◽  
Robert G. Presson ◽  
Nobuhiro Tanabe ◽  
Eric M. Jaryszak ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Average Distance ◽  
Substantial Part ◽  
Alveolar Wall ◽  
Capillary Perfusion ◽  
Capillary Networks ◽  
Pulmonary Capillaries ◽  
Pulmonary Capillary ◽  
Alveolar Capillary

Pulmonary capillary perfusion within a single alveolar wall continually switches among segments, even when large-vessel hemodynamics are constant. The mechanism is unknown. We hypothesize that the continually varying size of plasma gaps between individual red blood cells affects the likelihood of capillary segment closure and the probability of cells changing directions at the next capillary junction. We assumed that an increase in hematocrit would decrease the average distance between red blood cells, thereby decreasing the switching at each capillary junction. To test this idea, we observed 26 individual alveolar capillary networks by using videomicroscopy of excised canine lung lobes that were perfused first at normal hematocrit (31–43%) and then at increased hematocrit (51–62%). The number of switches decreased by 38% during increased hematocrit ( P < 0.01). These results support the idea that a substantial part of flow switching among pulmonary capillaries is caused by the particulate nature of blood passing through a complex network of tubes with continuously varying hematocrit.

Neutrophil kinetics and lung injury

1987 ◽  
Vol 67 (4) ◽  
pp. 1249-1295 ◽  
Author(s):  
J. C. Hogg
Keyword(s):  
Complete Understanding ◽  
Pulmonary Capillaries ◽  
Activated Neutrophils ◽  
Neutrophil Adherence ◽  
Capillary Bed ◽  
Pass Through ◽  
And Migration ◽  
Pulmonary Microcirculation ◽  
Number Of Segments ◽  
Neutrophil Kinetics

The fact that the lung stores a large proportion of the marginated pool of neutrophils is a result of the anatomy of the pulmonary microcirculation. This capillary bed is made up of a network of a very large number of segments, many of which have smaller diameters than the neutrophils. Both neutrophils and erythrocytes must deform to pass through the capillary bed, but as the neutrophils are larger and less deformable, they pass through the segments more slowly. The slower movement of neutrophils through the pulmonary capillaries produces little obstruction to erythrocyte flow because the very large number of segments allows the erythrocytes to stream around those that are filled with neutrophils. The size of the marginated pool of neutrophils in the lung depends on the balance between forces that propel the neutrophils through the capillary segments and those that tend to retard them. Activation of the PMN both decreases their deformability and increases their adherence to endothelium, which results in increased numbers of neutrophils in the lung and a reduction in the number circulating in the blood. There is growing evidence that the adherence of the neutrophil to the endothelial cell is mediated by the CD omega 18 on the surface of the neutrophil. The absence of these proteins leads to lack of neutrophil adherence and migration, whereas factors that enhance adherence lead to increased expression of these glycoproteins. The fact that activated neutrophils can also damage normal tissue has led to several attractive hypotheses concerning the pathogenesis of lung diseases such as emphysema and the ARDS. Further elucidation of factors that cause cells to marginate in the pulmonary circulation and a more complete understanding of the factors that control their adherence to endothelium, migration into the interstitial and airspace, and phagocytic function will undoubtedly lead to a better understanding of both the physiology and pathology of the lung.

The nature of leukocyte shape changes in the pulmonary capillaries

1997 ◽  
Vol 273 (4) ◽  
pp. L733-L740 ◽  
Author(s):  
Darlene M. Redenbach ◽  
Dean English ◽  
James C. Hogg
Keyword(s):  
Blood Cells ◽  
White Blood Cells ◽  
Cell Polarization ◽  
Cell Counts ◽  
Pulmonary Capillaries ◽  
Size Discrepancy ◽  
Capillary Bed ◽  
Washout Curves ◽  
Shape Changes

The size discrepancy between leukocytes [white blood cells (WBCs)] and pulmonary capillaries requires WBCs to deform. We investigated the persistence of this deformation on cells leaving the capillary bed and the role played by the cytoskeleton. Isolated rabbit lungs were perfused in situ via the pulmonary artery with effluent fractions collected from the left ventricle. Washout curves from cell counts in each fraction confirmed that WBCs are preferentially retained over erythrocytes. WBC deformation present on exit from the circulation was compared with that present after recovery in paired fractions, fixed either immediately or 60 min later. These cells were compared with cells recovered from the capillary in perfused fixative or fixed in peripheral blood. Our results show that leukocyte deformation persisted after the cells exited the pulmonary circulation. This deformation was associated with minimal submembranous F-actin staining, and microtubule distribution and cell polarization were unchanged. We conclude that cytoskeletal changes that occur during WBC deformation in the pulmonary capillaries are minimal and differ from those known to occur in actively migrating cells during chemotaxis.

The effect of prolonged perfusion with a membrane oxygenator (PPMO) on white blood cells

Perfusion ◽  
1994 ◽  
Vol 9 (1) ◽  
pp. 35-40 ◽  
Author(s):  
Per Bergman ◽  
Ali Belboul ◽  
Lars Göran Friberg ◽  
Najib Al-Khaja ◽  
Gösta Mellgren ◽  
...  
Keyword(s):  
Blood Cell ◽  
White Blood Cell ◽  
Blood Cells ◽  
White Blood Cells ◽  
White Cell ◽  
Mechanical Trauma ◽  
The Mean ◽  
Pass Through ◽  
Whole Blood Cells

Preserving the rheological properties of whole blood cells is vital for their smooth passage in the capillaries without causing blockage and disturbances in the microcirculation. To evaluate the effect of mechanical trauma on the rheology of white blood cells during prolonged perfusion with membrane oxygenation (PPMO), 16 in vitro experiments were conducted for 72 hours. The St George Carrimed Filtrometer was used to estimate the plasma white cell filtration rates (P-WFR). Also an in vitro estimation of the ability of individual cells to pass through capillaries, the white blood cell clogging rate (WBC-CR), the number of clogging particles (WBC-CP), the total white blood cell count (T-WBC) and two in vitro estimations to assess the effect of aggregates and stiff cells in blocking the microcirculation were performed. The traumatized white cells reduced their mean P-WFR by 37% ± 9, 72% ± 2 and 76% ± 2 at 24, 48 and 72 hours respectively (p < 0.001). The mean WBC-CR was increased to 15.2 ± 1.5, 32.6 ± 2.2 and 40.3 ± 8.3 x 102%/ml at 24, 48 and 72 hours respectively (p < 0.001). The mean WBC-CP was increased to 6.6 ± 1.5, 9.7 ± 1.2 and 13.9 ± 2.1 x 106/ml at 24 hours (p < 0.05), 48 and 72 hours respectively (p < 0.001). The T-WBC was decreased to 55% ± 0.3, 23% ± 0.2 and 14% ± 0.1 at 24,48 and 72 hours respectively (p < 0.001). This study showed a serious loss in white cell rheology during PPMO, which may contribute to the plugging effect of the microvessels in clinical use and may explain the organ dysfunction seen during ECMO on the basis of inadequate tissue oxygenation and nutrition due to areas of reduced perfusion, which results in increased frequency of morbidity.

Effect of zymosan-activated plasma on the deformability of rabbit polymorphonuclear leukocytes

1992 ◽  
Vol 73 (4) ◽  
pp. 1370-1376 ◽  
Author(s):  
H. Inano ◽  
D. English ◽  
C. M. Doerschuk
Keyword(s):  
Polymorphonuclear Leukocytes ◽  
Cytochalasin B ◽  
Rapid Decrease ◽  
Microtubule Assembly ◽  
Constant Flow Rate ◽  
Narrow Capillary ◽  
Capillary Bed ◽  
Pass Through

Intravascular infusion of inflammatory mediators causes a sudden neutropenia due to the sequestration of polymorphonuclear leukocytes (PMN) within the microvasculature of the lung and other organs. This sequestration could be due to a decrease in the ability of PMN to deform and pass through the narrow capillary bed. The purpose of this study was to determine if the complement fragments present in zymosan-activated plasma (ZAP) caused a rapid stiffening of PMN. The PMN deformability was determined by measuring the pressure required to pass PMN through a polycarbonate filter containing 5-micron pores at a constant flow rate as well as the extraction of PMN compared with red blood cells and 125I-labeled albumin by the filter. The role of the cytoskeleton in PMN deformation was examined in studies where F-actin formation was inhibited using cytochalasin B or microtubule assembly was inhibited using colchicine. The results showed that treatment with ZAP induced a rapid decrease in PMN deformability. Inhibiting the formation of F-actin made the unstimulated PMN more deformable and reduced the stiffening induced by ZAP. In contrast, inhibition of microtubule reassembly did not alter either normal deformability or the ZAP-induced decrease in deformability. In vivo, colchicine increased normal PMN margination but did not inhibit the rapid sequestration of PMN induced by infusion of ZAP. These studies indicate that ZAP induces a rapid decrease in PMN deformability that is mediated through the cytoskeleton. They suggest that this decrease is due to the polymerization of F-actin.

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