Platelets support pulmonary recruitment of neutrophils in abdominal sepsis.
OBJECTIVE
Recent findings indicate that platelets not only regulate thrombosis and hemostasis but may also be involved in proinflammatory activities. Herein, we hypothesized that platelets may play a role in sepsis by activating and priming circulating neutrophils for subsequent recruitment into the lung.


METHODS
Prospective experimental study.


METHODS
University Hospital Research Unit.


METHODS
Male C57BL/6 mice.


METHODS
Lung edema, bronchoalveolar infiltration of neutrophils, levels of myeloperoxidase, expression and function of membrane-activated complex-1 (Mac-1) on neutrophils and the CXC chemokines, macrophage inflammatory protein-2, and cytokine-induced neutrophil chemoattractant were determined after cecal ligation and puncture (CLP). Mice received a platelet-depleting antibody as well as antibodies directed against P-selectin glycoprotein-ligand-1 and Mac-1 before CLP induction.


RESULTS
CLP caused significant pulmonary damage characterized by neutrophil infiltration, increased levels of CXC chemokines, and edema formation in the lung. Furthermore, CLP up-regulated Mac-1 expression on neutrophils and increased the number of neutrophils binding platelets in the circulation. Interestingly, depletion of platelets reduced CLP-induced edema and neutrophil recruitment in the bronchoalveolar space by >60%. Furthermore, depletion of platelets reduced Mac-1 expression on neutrophils. On the other hand, inhibition of P-selectin glycoprotein-ligand-1 abolished CLP-induced neutrophil-platelet aggregation but had no effect on neutrophil expression of Mac-1.


CONCLUSIONS
These data demonstrate that platelets play a key role in regulating infiltration of neutrophils and edema formation in the lung via upregulation of Mac-1 in abdominal sepsis.
Asaduzzaman
Muhammad
M
Department of Surgery, Malmö University Hospital, Lund University, Malmö, Sweden.
Lavasani
Shahram
S
Rahman
Milladur
M
Zhang
Su
S
Braun
Oscar O
OO
Jeppsson
Bengt
B
Thorlacius
Henrik
H
D000005:Abdomen; D000818:Animals; D001792:Blood Platelets / Q000502:physiology*; D008168:Lung / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D011654:Pulmonary Edema / Q000276:immunology*; D018805:Sepsis / Q000276:immunology*