Mast cell-independent impairment of host defense and muscle contraction inT. spiralis-infected W/WVmice

2001 ◽  
Vol 280 (4) ◽  
pp. G640-G648 ◽  
Author(s):  
Bruce A. Vallance ◽  
Patricia A. Blennerhassett ◽  
Jan D. Huizinga ◽  
Stephen M. Collins
Keyword(s):  
Mast Cells ◽  
Tissue Damage ◽  
Host Response ◽  
Contractile Response ◽  
Trichinella Spiralis ◽  
Tissue Injury ◽  
Contractile Activity ◽  
Wild Type ◽  
Worm Expulsion

In response to nematode infection, the host presumably attempts to create an unfavorable environment to prevent larval penetration of the host and to expedite parasite expulsion from the gut. In this study, we have used W/WVmice with or without mast cells after bone marrow reconstitution (BMR-W/WV) to examine the role of mast cells in the host response. W/WV, BMR-W/WV, and wild-type (+/+) mice were infected with Trichinella spiralis. Infected W/WVmice exhibited less tissue damage and experienced a delay in worm expulsion and a greater degree of larval penetration of the gut leading to encystment in skeletal muscle. Tissue injury was greater and worm expulsion was normalized in BMR-W/WVmice, but larval penetration remained unchanged. Spontaneous contractile activity of jejunal muscle was disrupted in W/WVmice, as was the contractile response to carbachol. These abnormalities were also present in BMR-W/WVmice. These results indicate that mast cells mediate tissue damage and contribute to the timely expulsion of nematodes from the gut during primary infection.

CCSP modulates airway dysfunction and host responses in an Ova-challenged mouse model

2001 ◽  
Vol 281 (5) ◽  
pp. L1303-L1311 ◽  
Author(s):  
Shan-Ze Wang ◽  
Cynthia L. Rosenberger ◽  
Teresa M. Espindola ◽  
Edward G. Barrett ◽  
Yohannes Tesfaigzi ◽  
...  
Keyword(s):  
Airway Epithelium ◽  
Host Response ◽  
Secretory Protein ◽  
Allergic Airway Disease ◽  
Clara Cell ◽  
Myeloperoxidase Activity ◽  
Wild Type ◽  
Airway Reactivity ◽  
Mucus Production

Clara cell secretory protein (CCSP) is synthesized by nonciliated bronchiolar cells in the lung and modulates lung inflammation to infection. To determine the role of CCSP in the host response to allergic airway disease, CCSP-deficient [(−/−)] mice were immunized twice with ovalbumin (Ova) and challenged by Ova (2 or 5 mg/m3) aerosol. After 2, 3, and 5 days of Ova aerosol challenge (6 h/day), airway reactivity was increased in CCSP(−/−) mice compared with wild-type [CCSP(+/+)] mice. Neutrophils were markedly increased in the bronchoalveolar lavage fluid of CCSP(−/−) Ova mice, coinciding with increased myeloperoxidase activity and macrophage inflammatory protein-2 levels. Lung histopathology and inflammation were increased in CCSP(−/−) compared with wild-type mice after Ova challenge. Mucus production, as assessed by histological staining, was increased in the airway epithelium of CCSP(−/−) Ova mice compared with that in CCSP(+/+) Ova mice. These data suggest a role for CCSP in airway reactivity and the host response to allergic airway inflammation and provide further evidence for the role of the airway epithelium in regulating airway responses in allergic disease.

Role of common cytokine receptor γ chain (γc)– and Jak3-dependent signaling in the proliferation and survival of murine mast cells

Blood ◽  
2000 ◽  
Vol 96 (6) ◽  
pp. 2172-2180 ◽  
Author(s):  
Kotaro Suzuki ◽  
Hiroshi Nakajima ◽  
Norihiko Watanabe ◽  
Shin-ichiro Kagami ◽  
Akira Suto ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mast Cells ◽  
Cytokine Receptor ◽  
Type I ◽  
Dependent Manner ◽  
Type Ii ◽  
Wild Type ◽  
Peritoneal Mast Cells ◽  
The Common

Abstract The regulatory roles of the common cytokine receptor γ chain (γc)– and Jak3-dependent signaling in the proliferation and survival of mast cells were determined using γc-deficient (γc−) and Jak3-deficient (Jak3−) mice. Although the mast cells in γc− and Jak3− mice were morphologically indistinguishable from those in wild-type mice, the number of peritoneal mast cells was decreased in γc− and Jak3− mice as compared with that in wild-type mice. Among γc-related cytokines, interleukin (IL)-4 and IL-9, but not IL-2, IL-7, or IL-15, enhanced the proliferation and survival of bone marrow–derived mast cells (BMMCs) from wild-type mice. However, the effects of IL-4 and IL-9 were absent in BMMCs from γc− and Jak3−mice. In addition, IL-4Rα, γc, and Jak3, but not IL-2Rβ or IL-7Rα, were expressed in BMMCs. In contrast, IL-13 did not significantly induce the proliferation and survival of BMMCs even from wild-type mice, and IL-13Rα1 was not expressed in BMMCs. Furthermore, IL-4 phosphorylated the 65-kd isoform of Stat6 in BMMCs from wild-type mice but not from γc− and Jak3− mice. These results indicate that γc- and Jak3-dependent signaling is essential for IL-4– and IL-9–induced proliferation and survival of murine mast cells, that the effects of IL-4 are mediated by type I IL-4R and that type II IL-4R is absent on mast cells, and that IL-4 phosphorylates the 65-kd isoform of Stat6 in mast cells in a γc- and Jak3-dependent manner.

Host–parasite interactions in rodent nematode infections

2003 ◽  
Vol 77 (2) ◽  
pp. 125-131 ◽  
Author(s):  
Y.R. Mahida
Keyword(s):  
Neutralizing Antibodies ◽  
Host Response ◽  
Trichinella Spiralis ◽  
Host Responses ◽  
Nippostrongylus Brasiliensis ◽  
Trichuris Muris ◽  
Epithelial Phenotype ◽  
Worm Expulsion ◽  
Genetically Manipulated ◽  
Host Parasite

AbstractIn rodents,Trichinella spiralisandNippostrongylus brasiliensisinfect the small intestine andTrichuris murisresides in the colon. The intestinal host response in these animals is characterized by changes in mucosal architecture and inflammation and is associated with worm expulsion. The requirement of T cell-mediated host response in worm expulsion has been demonstrated over many years. Subsequent studies have shown that Th2-type, but not Th1-type, responses mediate resistance to the nematodes. Investigations using neutralizing antibodies and genetically manipulated mice have characterized the contribution of individual Th2-type cytokines in not only worm expulsion, but also specific cellular changes that occur in the mucosa, such as alterations in epithelial phenotype and smooth muscle. There is also increasing appreciation of the contribution of non-bone marrow-derived cells in innate and adaptive host responses in these models.

scholarly journals Role of Tachykinins in the Host Response to Murine Gammaherpesvirus Infection

2001 ◽  
Vol 75 (21) ◽  
pp. 10467-10471 ◽  
Author(s):  
Catherine M. Payne ◽  
Caroline J. Heggie ◽  
David G. Brownstein ◽  
James P. Stewart ◽  
John P. Quinn
Keyword(s):  
Virus Infection ◽  
Host Response ◽  
Infectious Virus ◽  
Inflammatory Cells ◽  
Direct Influence ◽  
Wild Type ◽  
Murine Gammaherpesvirus ◽  
Latently Infected ◽  
Infected Cells

ABSTRACT Tachykinins function not only as neurotransmitters but also as immunological mediators. We used infection of tachykinin-deficient (PPT-A −/−) mice and wild-type controls with murine gammaherpesvirus to assess the role of tachykinins in the host response to a virus infection. Although infection was ultimately controlled in PPT-A −/− mice, there were higher titers of infectious virus in the lungs, accompanied by a more rapid influx of inflammatory cells. Clearance of latently infected cells from the spleen was also delayed. This is the first report of the direct influence of tachykinins in the host response to a virus infection.

Distinct roles of PMCA isoforms in Ca2+ homeostasis of bladder smooth muscle: evidence from PMCA gene-ablated mice

2007 ◽  
Vol 292 (1) ◽  
pp. C423-C431 ◽  
Author(s):  
Li Liu ◽  
Yukisato Ishida ◽  
Gbolahan Okunade ◽  
Gail J. Pyne-Geithman ◽  
Gary E. Shull ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Plasma Membrane ◽  
Contractile Response ◽  
Signal Transduction Pathway ◽  
Transduction Pathway ◽  
Wild Type ◽  
Bladder Smooth Muscle

We previously showed that plasma membrane Ca2+-ATPase (PMCA) activity accounted for 25–30% of relaxation in bladder smooth muscle ( 8 ). Among the four PMCA isoforms only PMCA1 and PMCA4 are expressed in smooth muscle. To address the role of these isoforms, we measured cytosolic Ca2+ ([Ca2+]i) using fura-PE3 and simultaneously measured contractility in bladder smooth muscle from wild-type (WT), Pmca1+/−, Pmca4+/−, Pmca4−/−, and Pmca1+/− Pmca4−/− mice. There were no differences in basal [Ca2+]i values between bladder preparations. KCl (80 mM) elicited both larger forces (150–190%) and increases in [Ca2+]i (130–180%) in smooth muscle from Pmca1+/− and Pmca1+/− Pmca4−/− bladders than those in WT or Pmca4−/−. The responses to carbachol (CCh: 10 μM) were also greater in Pmca1+/− (120–150%) than in WT bladders. In contrast, the responses in Pmca4−/− and Pmca1+/− Pmca4−/− bladders to CCh were significantly smaller (40–50%) than WT. The rise in half-times of force and [Ca2+]i increases in response to KCl and CCh, and the concomitant half-times of their decrease upon washout of agonist were prolonged in Pmca4−/− (130–190%) and Pmca1+/− Pmca4−/− (120–250%) bladders, but not in Pmca1+/− bladders with respect to WT. Our evidence indicates distinct isoform functions with the PMCA1 isoform involved in overall Ca2+ clearance, while PMCA4 is essential for the [Ca2+]i increase and contractile response to the CCh receptor-mediated signal transduction pathway.

scholarly journals Renal vasoconstriction by vasopressin V1a receptors is modulated by nitric oxide, prostanoids, and superoxide but not the ADP ribosyl cyclase CD38

2014 ◽  
Vol 306 (10) ◽  
pp. F1143-F1154 ◽  
Author(s):  
Nicholas G. Moss ◽  
Tayler E. Kopple ◽  
William J. Arendshorst
Keyword(s):  
Nitric Oxide ◽  
Contractile Response ◽  
Receptor Activation ◽  
Wild Type ◽  
Renal Vasoconstriction ◽  
Adp Ribosyl Cyclase ◽  
Cyclic Adp Ribose ◽  
Renal Vascular ◽  
Dose Dependent

Renal blood flow (RBF) responses to arginine vasopressin (AVP) were tested in anesthetized wild-type (WT) and CD38−/− mice that lack the major calcium-mobilizing second messenger cyclic ADP ribose. AVP (3–25 ng) injected intravenously produced dose-dependent decreases in RBF, reaching a maximum of 25 ± 2% below basal RBF in WT and 27 ± 2% in CD38−/− mice with 25 ng of AVP. Renal vascular resistance (RVR) increased 75 ± 6% and 78 ± 6% in WT and CD38−/− mice. Inhibition of nitric oxide (NO) synthase with nitro-l-arginine methyl ester (l-NAME) increased the maximum RVR response to AVP to 308 ± 76% in WT and 388 ± 81% in CD38−/− ( P < 0.001 for both). Cyclooxygenase inhibition with indomethacin increased the maximum RVR response to 125 ± 15% in WT and 120 ± 14% in CD38−/− mice ( P < 0.001, <0.05). Superoxide suppression with tempol inhibited the maximum RVR response to AVP by 38% in both strains ( P < 0.005) but was ineffective when administered after l-NAME. The rate of RBF recovery (relaxation) after AVP was slowed by l-NAME and indomethacin ( P < 0.001, <0.005) but was unchanged by tempol. All vascular responses to AVP were abolished by an AVP V1a receptor antagonist. A V2 receptor agonist or antagonist had no effect on AVP-induced renal vasoconstriction. Taken together, the results indicate that renal vasoconstriction by AVP in the mouse is strongly buffered by vasodilatory actions of NO and prostanoids. The vasoconstriction depends on V1a receptor activation without involvement of CD38 or concomitant vasodilatation by V2 receptors. The role of superoxide is to enhance the contractile response to AVP, most likely by reducing the availability of NO rather than directly stimulating intracellular contraction signaling pathways.

scholarly journals Auxin, abscisic acid and jasmonate are the central players in rice sheath rot caused by Sarocladium oryzae and Pseudomonas fuscovaginae

2020 ◽  
Author(s):  
Kaat Peeters ◽  
Maarten Ameye ◽  
Kristof Demeestere ◽  
Kris Audenaert ◽  
Monica Hofte
Keyword(s):  
Abscisic Acid ◽  
Host Response ◽  
Wild Type ◽  
Yield Parameters ◽  
Mutant Strains ◽  
Rice Disease ◽  
Membrane Bound ◽  
Helvolic Acid ◽  
Sheath Rot

Abstract Sheath rot is an emerging rice disease that causes severe yield losses worldwide. The main causal agents are the toxin producers Sarocladium oryzae and Pseudomonas fuscovaginae. The fungus S. oryzae produces helvolic acid and cerulenin and the bacterium P. fuscovaginae produces cyclic lipopeptides. Helvolic acid and the lipopeptide, fuscopeptin, inhibit membrane-bound H+-ATPase pumps in the rice plant. To manage rice sheath rot, a better understanding of the host response and virulence strategies of the pathogens is required. This study investigated the interaction of the sheath rot pathogens with their host and the role of their toxins herein. Japonica rice was inoculated with high- and low-helvolic acid-producing S. oryzae isolates or with P. fuscovaginae wild type and fuscopeptin mutant strains. During infection, cerulenin, helvolic acid and the phytohormones abscisic acid, jasmonate, auxin and salicylic acid were quantified in the sheath. In addition, disease severity and grain yield parameters were assessed. Rice plants responded to high-toxin-producing S. oryzae and P. fuscovaginae strains with an increase in abscisic acid, jasmonate and auxin levels. We conclude that, for both pathogens, toxins play a core role during sheath rot infection. S. oryzae and P. fuscovaginae interact with their host in a similar way. This may explain why both sheath rot pathogens cause very similar symptoms despite their different nature.

The integrin alphavbeta6 is critical for keratinocyte migration on both its known ligand, fibronectin, and on vitronectin

1998 ◽  
Vol 111 (15) ◽  
pp. 2189-2195 ◽  
Author(s):  
X. Huang ◽  
J. Wu ◽  
S. Spong ◽  
D. Sheppard
Keyword(s):  
Cell Migration ◽  
Tissue Injury ◽  
Critical Role ◽  
Cell Behavior ◽  
Wild Type ◽  
Migration Assays ◽  
And Migration ◽  
Hepatocyte Growth

The integrin alphavbeta6 is expressed on a variety of epithelial cells during dynamic processes including organogenesis, tissue injury and malignant transformation. However, because of the lack of tools to specifically inhibit the function of this integrin, little is known about its effects on cell behavior. To directly examine the role of this integrin in cell migration, we used keratinocytes derived from wild-type mice or mice expressing a null mutation in the beta6 subunit (beta6-/-) to perform migration assays in vitro. Migration on the known alphavbeta6 ligand, fibronectin was reduced in keratinocytes from beta6-/- mice. Interestingly, keratinocytes from beta6-/- mice also demonstrated markedly reduced migration on vitronectin, a protein not previously known to be a ligand for alphavbeta6. An anti-alphavbeta6 monoclonal antibody 10D5, generated by immunization of beta6-/- mice with murine keratinocytes, inhibited adhesion and migration of wild-type keratinocyte on both vitronectin and fibronectin to levels similar to those seen with keratinocytes from beta6-/- mice. alphavbeta6-mediated migration on both ligands was dramatically augmented by treatment with phorbol myrisate acetate (PMA) or with hepatocyte growth factor, and augmentation of migration by either stimulus could be abolished by the PKC inhibitor GF109203X, suggesting a critical role for PKC in enhancement of alphavbeta6-mediated cell migration.

Abstract 200: CD40 Signaling Mediates Postischemic Inflammation, Oxidative Stress, And Tissue Injury Following Focal Cerebral Ischemia

Stroke ◽  
2012 ◽  
Vol 43 (suppl_1) ◽  
Author(s):  
Rong Jin ◽  
Zifang Song ◽  
Shiyong Yu ◽  
Daniel J Daunis ◽  
Brittany S Hopkins ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Nadph Oxidase ◽  
Tissue Damage ◽  
Tissue Injury ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Dependent Manner ◽  
Wild Type ◽  
Cox 2

Rationale: Although CD40/CD40 ligand (CD40L) signaling has been implicated in clinical and experimental ischemic strokes, the underlying mechanisms are largely unclear. Objective: We investigated how CD40 participates in the cellular and molecular events underlying the postischemic inflammation and oxidative stress that may contribute to the tissue damage during cerebral ischemia. Methods and Results: Wild-type (WT, n=164) and CD40 knockout mice (n=132) were subjected to middle cerebral artery occlusion (MCAO, 60 minutes) followed by reperfusion. We found that ischemia/reperfusion induced CD40 expression in the brain in a time-dependent manner, primarily localized to the microvascular endothelial cells in the early phase (6h) and then to the activated microglia in the later time (24h). The adhesion and infiltration of neutrophils as well as the activation and expansion of microglia induced by ischemia/reperfusion were inhibited in CD40-/- mice, which were time-dependently correlated with suppressing nuclear factor-kB activation and proinflammatory cytokines (IL-1β, TNFα) and adhesion molecules (E- and P-selectin, ICAM-1,MCP-1). Infarct volumes and mortality were reduced in CD40-/- mice at 72h after ischemia/reperfusion. Treatment with an inhibitor of either NADPH oxidase or COX-2, the known enzymes that contributes to the tissue damage, reduced ischemic brain injury in wild-type mice, but not in CD40-/- mice. In contrast, treatment with an inhibitor of inducible nitric oxide synthase (iNOS) further reduced tissue injury in CD40-/- mice. Consistently, ischemia/reperfusion-induced upregulation of NADPH oxidase (Nox2, and Nox4) and COX-2, but not iNOS, were attenuated in CD40-/- mice. Conclusions: The findings unveil an essential role for CD40 in the regulation of early molecular and cellular events leading to postischemic inflammation. Inhibition of CD40 signaling may be a valuable therapeutic approach to counteract the deleterious effects of postischemic inflammation.

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