We have, with interest, read the recently published article by Pluskota et al. in The Journal of Immunology (1). The novel concept that ligand-induced engagement of both subunits of αMβ2 integrin leads to protein kinase B (PKB)-mediated neutrophil survival is exciting. We are in agreement with the finding that soluble fibrinogen can prolong neutrophil survival as has also been previously published (2, 3). We, however, would like to comment on two essential points:

First, we agree with the authors’ suggestion that fibrinogen does not induce signaling in normal resting neutrophils. We confirm that fibrinogen preparations devoid of von Willebrand factor, plasminogen, and fibronectin did not induce PKB, NF-κB, Erk, or intracellular Ca2+ signaling in neutrophils. The strategy to activate integrins with 1 nM PMA to facilitate fibrinogen-induced signaling complicates the interpretation of the results. We believe that the authors cannot exclude that the marked Erk and PKB signaling is a result of priming of PMA-induced signaling. In addition, their article might lead to the conclusion that the PKB pathway is essential for fibrinogen-induced neutrophil survival, but no data were presented.

Second, the consequence of these findings is that primed circulating neutrophils induced by local inflammatory conditions (4) are activated in the circulation by contact with physiological concentrations of soluble fibrinogen. This would amplify rather than inhibit the systemic inflammatory response, which is an undesired clinical condition in many inflammatory diseases.

In conclusion, it is unlikely that soluble fibrinogen induces proinflammatory signaling despite its clear proinflammatory properties in immobilized form.

Pluskota, E., D. A. Soloviev, D. Szpak, C. Weber, E. F. Plow.
. Neutrophil apoptosis: selective regulation by different ligands of integrin αMβ2.
J. Immunol.
Rubel, C., G. C. Fernandez, G. Dran, M. B. Bompadre, M. A. Isturiz, M. S. Palermo.
. Fibrinogen promotes neutrophil activation and delays apoptosis.
J. Immunol.
Rubel, C., S. Gomez, G. C. Fernandez, M. A. Isturiz, J. Caamano, M. S. Palermo.
. Fibrinogen-CD11b/CD18 interaction activates the NF-κB pathway and delays apoptosis in human neutrophils.
Eur. J. Immunol.
Oudijk, E. J., W. B. Gerritsen, E. H. Nijhuis, D. Kanters, B.L. Maesen, J. W. Lammers, L. Koenderman.
. Expression of priming-associated cellular markers on neutrophils during an exacerbation of COPD.
Respir Med.