scholarly journals In Vitro Bactericidal Capacity of Human Polymorphonuclear Leukocytes: Diminished Activity in Chronic Granulomatous Disease of Childhood *

1967 ◽  
Vol 46 (4) ◽  
pp. 668-679 ◽  
Author(s):  
P. G. Quie ◽  
J. G. White ◽  
B. Holmes ◽  
R. A. Good
Keyword(s):  
Chronic Granulomatous Disease ◽  
Polymorphonuclear Leukocytes ◽  
Granulomatous Disease ◽  
Bactericidal Capacity ◽  
Human Polymorphonuclear Leukocytes

STUDIES OF POLYMORPHONUCLEAR LEUKOCYTES FROM PATIENTS WITH CHRONIC GRANULOMATOUS DISEASE OF CHILDHOOD: BACTERICIDAL CAPACITY FOR STREPTOCOCCI

PEDIATRICS ◽  
1968 ◽  
Vol 41 (3) ◽  
pp. 591-599
Author(s):  
Edward L. Kaplan ◽  
Throstur Laxdal ◽  
Paul G. Quie
Keyword(s):  
Chronic Granulomatous Disease ◽  
Polymorphonuclear Leukocytes ◽  
Gram Negative Bacteria ◽  
Granulomatous Disease ◽  
Gram Negative ◽  
Modified Method ◽  
Bactericidal Capacity ◽  
Normal Manner ◽  
Streptococcal Species

Polymorphonuclear leukocytes (PMNs) from children with chronic granulomatous disease of childhood have been shown to readily phagocytize staphylococci and certain gram-negative bacteria, but they demonstrate an impaired intracellular bactericidal capacity for these organisms. The in vitro phagocytic and bactericidal capacities of PMNs from three patients with this disease for four species of streptococci (Streptococcus faecalis, Streptococcus viridans, microaerophlic streptococci, and Streptococcus pyogenes) were tested by the modified method of Maaloe. The PMNs obtained from the patients phagocytized and killed the four species of streptococci in a normal manner while still showing the defect for Staph. aureus and S. marcescens. Morphologic examination of coverslip preparations of PMNs revealed minimal post-phagocytic degranulation and vacuole formation when either staphylococci and serratia or the streptococcal species were tested. This suggests that different intracellular mechanisms may be responsible for the streptococcal killing. These observations are in accord with the clinical courses of these patients, who rarely have serious streptococcal infections in contrast to the frequent and life-threatening infections caused by staphylococci and some gram-negative bacteria.

BACTERICIDAL FUNCTION OF HUMAN POLYMORPHONUCLEAR LEUKOCYTES

PEDIATRICS ◽  
1972 ◽  
Vol 50 (2) ◽  
pp. 264-270
Author(s):  
Paul G. Quie
Keyword(s):  
Hydrogen Peroxide ◽  
Chronic Granulomatous Disease ◽  
Polymorphonuclear Leukocytes ◽  
Bacterial Species ◽  
Bacterial Flora ◽  
Granulomatous Disease ◽  
Serum Factors ◽  
Gram Negative ◽  
Increased Risk ◽  
Human Polymorphonuclear Leukocytes

Serum from most normal persons contains specific antibodies which react with common bacterial species preparing their surfaces so that phagocytosis by leukocytes can take place. The Fab part of these antibodies reacts with immunologic specificity with antigens on the surface of bacteria. Another part of the immunoglobulin molecule termed the Fc portion is activated during the attachment of the Fab portion to bacteria and becomes a site for attachment of bacteria to receptors on the surface of phagocytic cells. This activity is greatly amplified by heat-labile serum factors. Normally bacteria are rapidly killed by human polymorphonuclear leukocytes after engulfment occurs. However staphylococci and gram-negative species of bacteria survive in the leukocytes of patients with the syndrome "Chronic Granulomatous Disease of Childhood." These patients have suffered recurrent severe infections with bacterial species that are part of the body's resident bacterial flora. By contrast these patients are not at increased risk to infection from such pyogenic bacterial species as group A streptococci or pneumococci. The leukocytes from patients with chronic granulomatous disease produce little hydrogen peroxide during phagocytosis. Catalase-producing staphylococci and gram-negative bacteria are not killed, but hydrogen peroxide-producing streptococci and pneumococci are killed. A normal metabolic response to phagocytosis as well as release of lysosonial factors are essential for the bactericidal activity of human polymorphonuclear leukocytes.

scholarly journals The biochemical basis of nitroblue tetrazolium reduction in normal human and chronic granulomatous disease polymorphonuclear leukocytes

Blood ◽  
1976 ◽  
Vol 48 (2) ◽  
pp. 309-313 ◽  
Author(s):  
RL Baehner ◽  
LA Boxer ◽  
J Davis
Keyword(s):  
Chronic Granulomatous Disease ◽  
Polymorphonuclear Leukocytes ◽  
Nitroblue Tetrazolium ◽  
Granulomatous Disease ◽  
Biochemical Basis ◽  
Nitroblue Tetrazolium Reduction ◽  
Normal Human ◽  
Nbt Reduction ◽  
Human Polymorphonuclear Leukocytes ◽  
Tetrazolium Reduction

Normal human polymorphonuclear leukocytes (PMN) placed in anaerobic chambers reaching pO2's of less than 5 mm Hg fail to generate O2-, iodinate ingested particles, and stimulate glucose-1–14C oxidation through the hexose monophosphate shunt. The observation that anaerobic cells are incapable of generating O2- or reducing nitroblue tetrazolium (NBT) to formazan supports the idea that NBT reduction in phagocytizing PMN is due exclusively to oxygen-dependent O2- generating oxidase which is deficient in chronic granulomatous disease leukocytes, despite their hyperphagocytic capacity.

scholarly journals The biochemical basis of nitroblue tetrazolium reduction in normal human and chronic granulomatous disease polymorphonuclear leukocytes

Blood ◽  
1976 ◽  
Vol 48 (2) ◽  
pp. 309-313 ◽  
Author(s):  
RL Baehner ◽  
LA Boxer ◽  
J Davis
Keyword(s):  
Chronic Granulomatous Disease ◽  
Polymorphonuclear Leukocytes ◽  
Nitroblue Tetrazolium ◽  
Granulomatous Disease ◽  
Biochemical Basis ◽  
Nitroblue Tetrazolium Reduction ◽  
Normal Human ◽  
Nbt Reduction ◽  
Human Polymorphonuclear Leukocytes ◽  
Tetrazolium Reduction

Abstract Normal human polymorphonuclear leukocytes (PMN) placed in anaerobic chambers reaching pO2's of less than 5 mm Hg fail to generate O2-, iodinate ingested particles, and stimulate glucose-1–14C oxidation through the hexose monophosphate shunt. The observation that anaerobic cells are incapable of generating O2- or reducing nitroblue tetrazolium (NBT) to formazan supports the idea that NBT reduction in phagocytizing PMN is due exclusively to oxygen-dependent O2- generating oxidase which is deficient in chronic granulomatous disease leukocytes, despite their hyperphagocytic capacity.

The Use of the Vitality and Chemotaxis of Human Polymorphonuclear Leukocytes for the In Vitro Estimation of the Acute Toxicity of the First Ten Chemicals from the MEIC List

1993 ◽  
Vol 21 (1) ◽  
pp. 73-80
Author(s):  
Matteo Valentino ◽  
Francesca Monaco ◽  
Maria Antonietta Pizzichini ◽  
Mario Governa
Keyword(s):  
Ethidium Bromide ◽  
Polymorphonuclear Leukocytes ◽  
Rank Correlation ◽  
Fluorescein Diacetate ◽  
Live Cells ◽  
In Vitro Toxicity ◽  
Ic50 Values ◽  
Acute Cytotoxicity ◽  
Human Polymorphonuclear Leukocytes

The acute cytotoxicity of the first ten MEIC chemicals has been estimated by others in various cell lines. In the present investigation, isolated human polymorphonuclear leukocytes (PMN) from ten healthy non-smoking laboratory personnel were used to assess in vitro toxicity of the same chemicals. The cells were treated with different concentrations of the respective chemicals for three hours and their vitality and chemotaxis were tested. Vitality was measured by fluorescence microscopy after the addition of fluorescein diacetate and ethidium bromide. Living cells which took up and hydrolysed fluorescein diacetate, and dead cells, stained by ethidium bromide, were counted and the percentage of live cells was calculated. Locomotion stimulated by the chemotactic peptide formyl-methionyl-leucyl-phenylalanine (F-MLP), was measured in blind-well Boyden chambers and a chemotactic index was calculated. The results were mathematically transformed to produce a linear curve, and then fitted by the linear least squares procedure, from which LC50 and IC50 values were obtained by interpolation. All the chemicals decreased the vitality and inhibited the chemotaxis of the PMN. Obviously the chemotactic test was more sensitive than the vitality one. A correlation (r = 0.933) was found between vitality and chemotaxis inhibition. Spearman rank correlation analysis revealed significant correlations between our results and those from in vitro experiments conducted in other laboratories, as well as with data concerning mouse, rat and human lethal doses.

NORMAL GRANULOCYTE INFUSION THERAPY FOR ASPERGILLOSIS IN CHRONIC GRANULOMATOUS DISEASE

PEDIATRICS ◽  
1973 ◽  
Vol 51 (2) ◽  
pp. 230-233
Author(s):  
Andrew A. Raubitschek ◽  
Alan S. Levin ◽  
Daniel P. Stites ◽  
Edward B. Shaw ◽  
H. Hugh Fudenberg
Keyword(s):  
Adverse Effects ◽  
Chronic Granulomatous Disease ◽  
Blood Cells ◽  
White Blood Cells ◽  
Infusion Therapy ◽  
Granulomatous Disease ◽  
Transient Improvement ◽  
Life Threatening ◽  
Granulocyte Function

An 8-year-old boy with chronic granulomatous disease (CGD) was admitted in moribund condition with aspergillus pneumonia. Because of the gravity of the situation, normal granulocyte infusions were used as adjuncts to the more conventional antimicrobial therapy. White blood cells, derived from a total of 58 units of whole blood obtained by leukophoresis of the father, were given in two separate doses. The first dose, totaling 2.8 x 1010 granulocytes, was coincident with significant improvement, and the second, totaling 3.0 x 1010 granulocytes, was coincident with the onset of clinical improvement and interim recovery. Transient improvement in in vitro granulocyte function was noted in cells taken from the patient's blood immediately after infusion. No adverse effects of the infusions were noted in either the patient or the donor. Although it is impossible to divorce the therapeutic effect of the granulocyte infusions from the more conventional therapy, we conclude that normal granulocyte infusions can be considered a valid adjunct in children with CGD who are suffering from a life-threatening infection.

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