title: CCL2, a product of mice early after systemic inflammatory response syndrome (SIRS), induces alternatively activated macrophages capable of impairing antibacterial resistance of SIRS mice.
abstract: Infection associated with systemic inflammatory response syndrome (SIRS) is a major cause of morbidity and mortality in patients with major surgery, polytrauma, and severe burn injury. In previous studies, mice with severe pancreatitis (a mouse model of SIRS, SIRS mice) have been shown to be greatly susceptible to various infections. In the present study, a mechanism involved in the impaired resistance of SIRS mice to infectious complications was investigated. Sera from SIRS mice impaired the resistance of normal mice to infectious complications induced by cecal ligation and puncture (CLP). CC chemokine ligand 2 (CCL2) was detected in sera of SIRS mice. Resident macrophages (RMphi) cultured with SIRS mouse sera converted to alternatively activated macrophages (AAMphi), which were also demonstrated in mice treated with recombinant murine CCL2. However, AAMphi were not demonstrated in mice injected with SIRS mouse sera and anti-CCL2 monoclonal antibody (mAb) in combination. Furthermore, normal mice that received SIRS mouse sera and anti-CCL2 mAb resisted CLP-induced infectious complications. These results indicate that the resistance of SIRS mice to infectious complications is impaired by AAMphi generated from RMphi in response to SIRS-associated CCL2 production.
authors.affiliation: Department of Internal Medicine, 301 University Boulevard, Galveston, TX 77555-0435, USA.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsuda
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Makiko
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.forename: Fujio
authors.initials: F
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D018932:Chemokine CCL2 / Q000378:metabolism*; D004195:Disease Models, Animal; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D010195:Pancreatitis / Q000378:metabolism; D018746:Systemic Inflammatory Response Syndrome / Q000378:metabolism*
chemical_list: C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2