Protection against lethal bacterial infection in mice by monocyte-chemotactic and -activating factor

Abstract

Chemotactic factors regulate the recruitment of neutrophils, lymphocytes, or monocytes-macrophages to infectious and inflammatory sites. The purpose of this study was to determine whether monocyte-chemotactic and -activating factor (MCAF [MCP-1I, aJE gene product) also influences the host defense mechanism against microbial infection. We evaluated the effect of recombinant human MCAF on the survival rate of mice systemically infected with Pseudomonas aeruginosa or Salmonella typhimurium. The administration of 2.5 ,ug of MCAF 6 h before infection completely protected the mice from lethal infection. Mice with cyclophosphamideinduced leukopenia exhibiting increased susceptibility to P. aeruginosa were also endowed with resistance by the same dose of MCAF. Administration of MCAF at -6 h was critical, since MCAF given either earlier or later than -6 h failed to rescue mice from lethal infection. The in vivo effect on the survival of mice paralleled the reduced recovery of viable P. aeruginosa or S. typhimurium from the peritoneal cavity, i.e., the number of recovered bacteria from the MCAF (2.5 ,ug per mouse)-treated mice was reduced to less than 2% of control mice for P. aeruginosa and 4% of control mice for S. typhimurium at 24 h. Since MCAF exhibited chemotaxis on murine macrophages as well as enhanced phagocytosis and killing of bacteria in vitro, the activation of macrophages, followed by the recruitment into the peritoneal cavity, is responsible for eliminating bacteria and thus enhancing the survival rate.

Significant Involvement of CCL2 (MCP‐1) in Inflammatory Disorders of the Lung

“…While CCL2 may contribute to acute lung injury and the fibroproliferative lung complication in patients with ARDS by monocyte recruitment and activation, inhibition of CCL2 in these patients could result in more dire circumstances. This is supported by observations in which administration of CCL2 attenuated mortality in animal models of sepsis (59). As sepsis is the most common underlying condition in patients with ARDS (55), it is possible that endogenous CCL2 inhibition might paradoxically worsen mortality.…”

Oncostatin M decreases interleukin‐1 β secretion by human synovial fibroblasts and attenuates an acute inflammatory reaction in vivo

“…Released by activated synoviocytes in the pannus, CXCL8 is a major mediator of inflammation and joint destruction [54,55]. In contrast, CCL2 is involved in macrophage recruitment typically concurrent with the waning of granulocytes [56] and contributes to tissue reparative processes [57] as well as protecting against viral and bacterial infections [58,59]. Finally, although the role of IL-6 in inflammation appears complex and multi-faceted [60], it has been shown in vivo to induce the IL-1 receptor antagonist and the soluble TNF receptor p55, both of which attenuate inflammation [61].…”

Effects of variation in maternal carotenoid intake during gestation on offspring innate immune response in a matrotrophic viviparous reptile

“…The proportion of monocytes we observed suggests that maternal b-carotene intake during gestation may enhance offspring innate immune response at 2 days after birth (see Brevard 1994;Nakano et al 1994;Hughes et al 1997;Hughes 1999): a high proportion of monocytes is indicative Table 3. Summary of the statistical analyses of immune response in offspring at 2 weeks after birth: effects of maternal b-carotene intake during gestation, offspring b-carotene intake for 2 weeks after birth, injection treatment (i.e.…”

“…Furthermore, LPS stimulation can alter the proportion of different white blood cell types. For example, the proportion of monocytes increases (Selvaraj, Sampath & Sekar 2009;Nya & Austin 2010) because monocytes respond to bacteria (Tizard 1991;Nakano et al 1994). Therefore, a high proportion of monocytes after LPS injection are indicative of a strong innate immune response.…”