The role of platelet factor 4 in local and remote tissue damage in a mouse model of mesenteric ischemia/reperfusion injury.
The robust inflammatory response that occurs during ischemia reperfusion (IR) injury recruits factors from both the innate and adaptive immune systems. However the contribution of platelets and their products such as Platelet Factor 4 (PF4; CXCL4), during the pathogenesis of IR injury has not been thoroughly investigated. We show that a deficiency in PF4 protects mice from local and remote tissue damage after 30 minutes of mesenteric ischemia and 3 hours of reperfusion in PF4-/- mice compared to control B6 mice. This protection was independent from Ig or complement deposition in the tissues. However, neutrophil and monocyte infiltration were decreased in the lungs of PF4-/- mice compared with B6 control mice. Platelet-depleted B6 mice transfused with platelets from PF4-/- mice displayed reduced tissue damage compared with controls. In contrast, transfusion of B6 platelets into platelet depleted PF4-/- mice reconstituted damage in both intestine and lung tissues. We also show that PF4 may modulate the release of IgA. Interestingly, we show that PF4 expression on intestinal epithelial cells is increased after IR at both the mRNA and protein levels. In conclusion, these findings demonstrate that may PF4 represent an important mediator of local and remote tissue damage.
Rheumatology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, United States of America.
Peter H
PH
Lapchak
Antonis
A
Ioannou
Poonam
P
Rani
Linda A
LA
Lieberman
Kazuhisa
K
Yoshiya
Lakshmi
L
Kannan
Jurandir J
JJ
Dalle Lucca
M Anna
MA
Kowalska
George C
GC
Tsokos
D000818:Animals; D003165:Complement System Proteins / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D007136:Immunoglobulins / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D008638:Mesenteric Arteries / Q000473:pathology*; D008643:Mesentery / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D009000:Monocytes / Q000473:pathology; D020556:Neutrophil Infiltration; D010978:Platelet Factor 4 / Q000235:genetics / Q000378:metabolism*; D017713:Platelet Transfusion; D015427:Reperfusion Injury / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000628:therapy
D007136:Immunoglobulins; D010978:Platelet Factor 4; D003165:Complement System Proteins