Journal
JOURNAL OF EXPERIMENTAL MEDICINE
Volume 198, Issue 8, Pages 1243-1251Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20030906
Keywords
Shwartzman reaction; thrombosis; hemorrhage; cell adhesion molecules; innate immunity
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Funding
- NHLBI NIH HHS [P01 HL036110, HL-36110] Funding Source: Medline
- NIAID NIH HHS [AI-31599, AI-41144, R01 AI041144, P01 AI031599, U19 AI031599] Funding Source: Medline
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gp49B1 is expressed on mast cells and inhibits immunoglobulin E-dependent activation and inflammation in vivo. We now show that gp49B1 is expressed oil neutrophils and prevents neutrophil-dependent vascular injury in response to lipopolysaccharide (LPS). The intradermal (i.d.) injection of LPS into gp49B1-null (gp49B(-/-)) but not gp49B1-sufficient (gp49B(+/+)) mice elicited macroscopic hemorrhages by 24 h, which were preceded on microscopic analyses by significantly more intravascular thrombi (consisting of neutrophils, platelets, and fibrin) that occluded venules and by more tissue neutrophils than in gp49B(+/+) mice. However, there were no differences in the number of intact (nondegranulating) mast cells or the tissue levels of mediators that promote neutrophil recrititment. Hemorrhage was prevented by depleting neutrophils, blocking beta2 integrin-intercellular adhesion molecule 1 interactions, or inhibiting coagulation. These characteristics indicate that gp49B(-/-) mice are exquisitely sensitive to a local Shwartzman reaction (LSR) after a single i.d. injection of LPS, whereas in the classic LSR, a second exposure is required for increased beta2 integrin function, intravascular neutrophil aggregation, formation of occlusive thrombi, and hemorrhage. Moreover, LPS increased gp49B1 expression on neutrophils in vivo. The results suggest that gp49131 suppresses the LPS-induced increase in intravascular neutrophil adhesion, thereby providing critical innate protection against a pathologic response to a bacterial component.
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