Neutrophils chemokine/cytokine receptors

Neutrophils are the most abundant leukocytes in humans, comprising about two thirds of peripheral blood leukocytes. Upon tissue injury, they rapidly infiltrate injury sites and play an important role in innate immune responses. In addition, they also contribute to the development of adaptive immune responses by producing an array of cytokines and chemokines. Tissue infiltration of neutrophils is initiated by signals generated by the interaction between chemoattractants produced at sites of injury and their corresponding cell surface receptors. Classical chemoattractants, such as C5a, N-formyl-methionyl-leucyl-... 

Sato N, Ahuja SK, Quinones M, et al. CC chemokine receptor (CCR)2 is required for langerhans cell migration and localization of T helper cell type 1 (Thl)-inducing dendritic cells. Absence of CCR2 shifts the Leishmania major-resistant phenotype to a susceptible state dominated by Th2 cytokines, b cell outgrowth, and sustained neutrophilic inflammation. J Exp Med 2000 192(2) 205-218. 

In the last decade or so, another key facet of neutrophil biology has emerged, that is, the ability to express a sizeable number of genes whose products lie at the core of inflammatory and immune responses. These include growth factors, cell surface receptors, adhesion molecules, cytokines such as TNFa, IL-1 (3, IL-12, and TGF(3, and a wide array of chemokines such as IL-8, Groa, Mip-la/(3, Mip-3a/(3, IP-10, MIG, I-TAC, and others [reviewed in 2]. The production of inflammatory cytokines and chemokines by neutrophils is... 

IL-10, an important downregulator of inflammation, decreases levels of IL-12 mRNA and protein secretion by neutrophils [12], and has similar effects on secretion of chemokines such as MlP-la, MlP-ip, and lL-8 [58]. The inhibitory effect of lL-10 requires de novo protein synthesis and is therefore only apparent after several hours of in vitro culture [58]. Full PMN responsiveness to IL-10 is acquired only after exposure to LPS, and correlates with upregulation of the IL-lORl component of the lL-10 receptor complex [59]. Subsequent StatS tyrosine phosphorylation leads to inhibition of proinflamma-tory cytokines by still poorly defined mechanisms. 

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