An essential role of macrophage inflammatory protein 1alpha/CCL3 on the expression of host's innate immunities against infectious complications.
Sepsis was induced by well-controlled cecal ligation and puncture (CLP) in macrophage inflammatory protein 1alpha (MIP-1alpha)/CCL3 knockout (CCL3(-/-)) and severe combined immunodeficiency (SCID) mice. CCL3(-/-) mice and their littermates (CCL3(+/+) mice) treated with anti-CCL3 monoclonal antibodies were susceptible (0-20% survival) to CLP-induced sepsis, and CCL3(-/-) mice supplemented with recombinant (r)CCL3 (250 ng/mouse) and CCL3(+/+) mice were resistant (70-80% survival). The resistance of SCID mice to CLP was markedly improved by the rCCL3 administration (88% survival), and SCID mice treated with saline were shown to be middling resistant to the same CLP (45% survival). However, the resistance of SCID-M mice (SCID mice depleted of the macrophage function) to CLP was not improved by the rCCL3 administration (11% survival), and 41% of SCID-M mice reconstituted with normal peritoneal macrophages and 79% of SCID-M mice inoculated with CCL3-treated peritoneal macrophages survived. In addition, the resistance of SCID-MN mice (SCID mice depleted of functional macrophages and neutrophils) to CLP was improved by the inoculation of CCL3-treated macrophages (78% survival), and all of SCID-MN mice inoculated with CCL3-treated neutrophils died. CCL3 is shown to be essential to the host resistance against bacterial sepsis. Macrophages but not neutrophils are highlighted as the major effector cells when protective innate immunities against sepsis are improved by CCL3.
Takahashi
Hitoshi
H
Department of Internal Medicine, The University of Texas Medical Branch, Galveston 77555, USA.
Tashiro
Tsuguhiko
T
Miyazaki
Masaru
M
Kobayashi
Makiko
M
Pollard
Richard B
RB
Suzuki
Fujio
F
D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D003141:Communicable Diseases / Q000150:complications / Q000276:immunology* / Q000628:therapy; D004305:Dose-Response Relationship, Drug; D007113:Immunity, Innate / Q000187:drug effects; D019402:Macrophage Inflammatory Proteins / Q000276:immunology* / Q000502:physiology; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000637:transplantation; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010587:Phagocytosis / Q000187:drug effects; D018805:Sepsis / Q000276:immunology / Q000628:therapy
D000911:Antibodies, Monoclonal; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins