Platelet depletion in mice increases mortality after thermal injury.
Platelets play a fundamental role in maintaining hemostasis and have been shown to participate in innate and adaptive immunity. However, the role of platelets in the immune response to injury remains undefined. We tested the importance of platelets in the host response to serious injury in a newly developed platelet-deficient mouse model. Wild-type and platelet-depleted C57BL/6J mice underwent a 25% full-thickness total body surface area thermal or sham injury. Platelet-deficient mice showed survival of 51% at 48 hours after injury compared with 94% to 100% survival in experimental control mice (P < .001). Necropsy and histology ruled out hemorrhage and hypovolemia as causes of death. Percentages of peripheral blood monocytes (P < .01) and neutrophils (P < .05) were increased between 36 and 48 hours after thermal injury in platelet-deficient mice compared with control mice. Plasma levels of TNFalpha (P < .001), IL-6 (P < .001), and MCP-1 (P < .05) were also elevated by 24 hours whereas levels of TGFbeta(1) were reduced between 24 and 36 hours following injury in platelet-depleted mice (P < .001) compared with control mice. Our findings demonstrate for the first time that platelets play a critical protective role during the host response to injury. Moreover, our findings suggest that platelets and, more importantly, platelet-derived TGFbeta(1) modulate the systemic inflammatory response occurring after injury.
Fujimi
Satoshi
S
Julian and Eunice Cohen Laboratory for Surgical Research, Department of Surgery, Brigham and Women's Hospital, Boston, MA 02115, USA.
MacConmara
Malcolm P
MP
Maung
Adrian A
AA
Zang
Yan
Y
Mannick
John A
JA
Lederer
James A
JA
Lapchak
Peter H
PH
D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D018932:Chemokine CCL2 / Q000097:blood; D004195:Disease Models, Animal; D006358:Hot Temperature / Q000009:adverse effects*; D007249:Inflammation / Q000097:blood; D051379:Mice; D008810:Mice, Inbred C57BL; D010976:Platelet Count; D015996:Survival Rate; D016212:Transforming Growth Factor beta / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D014947:Wounds and Injuries / Q000097:blood* / Q000276:immunology / Q000401:mortality
D018932:Chemokine CCL2; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha