Chemokines constitute a family of chemoattractant cytokines which are subdivided into four families based on the number and spacing of the conserved cysteine residues in the N-terminus of the protein. Chemokines play a major role in selectively recruiting monocytes, neutrophils and lymphocytes as well as inducing chemotaxis through the activation of G-protein-coupled receptors (GPCR). Monocyte chemoattractant protein-1 (MCP-1/CCL2) is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages. Both CCL2 and its receptor CCR2 have been demonstrated to be induced and involved in a variety of diseases. Migration of monocytes from the blood stream across the vascular endothelium is required for routine immunological surveillance of tissues, as well as in response to inflammation. This review will discuss these biological processes and the structure and function of CCL2.

Pulmonary surfactant plays a variety of roles related to the regulation of immune function in the lung. Of particular interest in this regard is surfactant protein A (SP-A), a calcium-dependent lectin. We have reported previously that SP-A enhances concanavalin A-induced proliferation, and in this study we examined the secretion of tumor necrosis factor-alpha (TNF-alpha), interleukins 1 alpha, 1 beta, and 6, and interferon-gamma by human peripheral blood mononuclear cells. Levels of all of the cytokines except interferon-gamma were increased by SP-A. In rat peripheral blood cells, splenocytes, and alveolar macrophages we found a similar enhancement of TNF-alpha release by SP-A. In combinations of SP-A and surfactant lipids, the increased levels of TNF-alpha resulting from SP-A treatment decreased as the lipids increased. At higher relative concentrations of SP-A, the lipids had little or no effect. SP-A also enhanced the production of immunoglobulins A, G, and M by rat splenocytes. Levels of each isotype were increased severalfold over control levels. These data demonstrate that SP-A is capable of modulating immune cell function in the lung by regulating cytokine production and immunoglobulin secretion.

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Surfactant lipids inhibit cytokine production by immune cells, and surfactant protein A (SP-A) stimulates it. By enzyme-linked immunosorbent assay and mRNA blotting, we studied proinflammatory cytokine production by the monocytic cell line THP-1. SP-A caused increases in tumor necrosis factor (TNF)-alpha within 1 h, peaking at 4 h and then declining. Interleukin (IL)-1 beta increased and stayed elevated for 24 h. SP-A stimulated IL-8 also, peaking at 4 h, rapidly declining, and peaking again at 24 h. SP-A-dependent changes were detected for IL-6, but at higher SP-A doses. mRNA levels for TNF-alpha and IL-1 beta increased in response to SP-A, peaking within 2 h. The increases in TNF-alpha mRNA and protein induced by SP-A were inhibited by surfactant lipids. For IL-1 beta and IL-8, the lipids either had no inhibitory influence or inhibited less than for TNF-alpha. This suggests that the ability of macrophages to participate in inflammatory reactions is enhanced by SP-A alone or by mixtures of lipids and SP-A containing more SP-A than in normal surfactant, as occurs in many conditions leading to inflammation.