Macrophages secrete a novel heparin-binding protein with inflammatory and neutrophil chemokinetic properties.

Abstract

We report the identification and purification of a new inflammatory monokine synthesized by the macrophage tumor cell line RAW 264.7 in response to endotoxin. This monokine, which we term "macrophage inflammatory protein" (MIP), is a doublet with an apparent molecular mass of approximately 8,000 daltons on SDS-PAGE but forms aggregates of greater than 2 x 10(6) daltons as assessed by gel filtration. Partial NH2-terminal amino acid sequence data reveal no significant homology with any previously described protein. Although the monokine is anionic under physiological conditions, it is one of two major macrophage-secreted proteins that bind to heparin at high salt concentrations. At 100 ng/ml or greater, MIP is chemokinetic for human polymorphonuclear cells and triggers hydrogen peroxide production. Subcutaneous injection of 10 ng or greater of MIP into footpads of C3H/HeJ mice elicits an inflammatory response, characterized by neutrophil infiltration. These findings suggest that MIP is an endogenous mediator that may play a role in the host responses that occur during endotoxemia and other inflammatory events.

Antioxidants improve antibacterial function in hyperoxia-exposed macrophages

“…MIP-1α was originally identified as a product of endotoxin stimulated RAW264.7 macrophages [14,15]. It has been shown that MIP-1α contributes to lung leukocyte accumulation and acute lung injury in various animal models [16,17]. As shown in Figure 5, MIP-1α was increased by 40% following hyperoxic exposure (P<0.05).…”

Adipose tissue inflammation and liver fat in patients with highly active antiretroviral therapy-associated lipodystrophy

“…In rodents, CCL2 has been shown to contribute to insulin resistance (16,34) and to adipocyte dedifferentiation (34). CCL3 is a monokine produced by macrophages and involved in inflammation, acting as a chemoattractant and an activator of polymorphonuclear leukocytes (44). TNF-␣ is a proinflammatory and lipolytic cytokine overexpressed in obesity by tissue macrophages and able of inducing insulin resistance, at least in rodents and human cells in vitro (33).…”

Isolation and characterization of a macrophage-derived heparin-binding growth factor.

“…Other known macrophage-derived growth factors differ from MD-HBGF in that either they do not bind to heparin, e.g., TGF-f, TGF-a, TNF-a ( Figure 5); they are endothelial cell mitogens, e.g., TGF-a (Schreiber et al, 1986); or they are endothelial cell inhibitors (TGF-3, TNF-a) (Baird and Durkin, 1986;Heimark et al, 1986;Frater-Schroder et aL., 1987;Muller et aL, 1987;Schweigerer et aL, 1987). The macrophage inflammatory proteins (MIP), although heparin-binding, are low molecular weight (8 kDa) anionic polypeptides that are pyrogenic and chemotactic for leukocytes but do not appear to be mitogenic (Wolpe et aL., 1988;Wolpe et aL., 1989). The monocyte-derived growth factor described by Singh and Bonin (1988) is an anionic 40-kDa polypeptide.…”