Role of inducible nitric oxide synthase in the regulation of neutrophil migration in zymosan-induced inflammation

M. N. Ajuebor, L. Virág, R. J. Flower, M. Perretti, Csaba Szabo

Research output: Contribution to journalArticle

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Abstract

In the present study, by comparing the responses in wild-type mice and mice lacking the inducible (or type 2) nitric oxide synthase (iNOS), we investigated the role played by iNOS in the regulation of polymorphonuclear granulocyte (PMN) accumulation and chemokine production in the mouse peritoneal cavity in respOnSe to administration of zymosan (0.2 mg). Zymosan injection induced the production of nitric oxide, and triggered a time- dependent PMN immigration into the peritoneal cavity. This response was associated with increases in the level of the chemokines macrophage inflammatory protein (MIP)-1α, MIP-2, monocyte chemo-attractant protein (MCP)-1 and cytokine-induced neutrophil chemo-attractant (KC), as measured in the peritoneal cavities. Injection of zymosan also induced a time-dependent increase in the production of the antiinflammatory cytokine interleukin-10 (IL-10) in the peritoneal cavity. When comparing the response between wild- type and iNOS knockout (KO) mice, we observed that the low-level PMN accumulation measured at 1 hr was slightly but significantly increased in the absence of functional iNOS. On the other hand, the delayed response (2-4 hr after zymosan) of PMN accumulation was suppressed in the iNOS KO mice. The early enhancement of PMN infiltration in the iNOS-deficient mice was associated with increased peritoneal levels of MIP-2, KC and IL-10 proteins. The delayed suppression of PMN infiltration was associated with reduced MIP- 2 and IL-10 levels in the peritoneal cavity. The lack of iNOS did not affect the release of MIP-1α and MCP-1 at any of the time-points studied. The current data demonstrate that iNOS regulates the production of certain CXC (but not CC) proinflammatory chemokines, the production of IL-10 and exerts a biphasic regulatory effect on PMN accumulation in zymosan-induced acute inflammation.

Original languageEnglish (US)
Pages (from-to)625-630
Number of pages6
JournalImmunology
Volume95
Issue number4
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Zymosan
Nitric Oxide Synthase Type II
Granulocytes
Neutrophils
Peritoneal Cavity
Inflammation
Chemokine CXCL2
Interleukin-10
Macrophage Inflammatory Proteins
Chemokines
Knockout Mice
Monocytes
Cytokines
CC Chemokines
Injections
Proteins
Emigration and Immigration
Peritoneal Macrophages
Nitric Oxide
Anti-Inflammatory Agents

ASJC Scopus subject areas

  • Immunology

Cite this

Role of inducible nitric oxide synthase in the regulation of neutrophil migration in zymosan-induced inflammation. / Ajuebor, M. N.; Virág, L.; Flower, R. J.; Perretti, M.; Szabo, Csaba.

In: Immunology, Vol. 95, No. 4, 1998, p. 625-630.

Research output: Contribution to journalArticle

Ajuebor, M. N. ; Virág, L. ; Flower, R. J. ; Perretti, M. ; Szabo, Csaba. / Role of inducible nitric oxide synthase in the regulation of neutrophil migration in zymosan-induced inflammation. In: Immunology. 1998 ; Vol. 95, No. 4. pp. 625-630.
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