Apoptotic human cells inhibit migration of granulocytes via release of lactoferrin.
Apoptosis is a noninflammatory, programmed form of cell death. One mechanism underlying the non-phlogistic nature of the apoptosis program is the swift phagocytosis of the dying cells. How apoptotic cells attract mononuclear phagocytes and not granulocytes, the professional phagocytes that accumulate at sites of inflammation, has not been determined. Here, we show that apoptotic human cell lines of diverse lineages synthesize and secrete lactoferrin, a pleiotropic glycoprotein with known antiinflammatory properties. We further demonstrated that lactoferrin selectively inhibited migration of granulocytes but not mononuclear phagocytes, both in vitro and in vivo. Finally, we were able to attribute this antiinflammatory function of lactoferrin to its effects on granulocyte signaling pathways that regulate cell adhesion and motility. Together, our results identify lactoferrin as an antiinflammatory component of the apoptosis milieu and define what we believe to be a novel antiinflammatory property of lactoferrin: the ability to function as a negative regulator of granulocyte migration.
Bournazou
Irini
I
The University of Edinburgh/Medical Research Council (MRC) Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, UK.
Pound
John D
JD
Duffin
Rodger
R
Bournazos
Stylianos
S
Melville
Lynsey A
LA
Brown
Simon B
SB
Rossi
Adriano G
AG
Gregory
Christopher D
CD
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D039481:CD11b Antigen / Q000378:metabolism; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D048430:Cell Shape; D017077:Culture Media, Conditioned / Q000737:chemistry; D006098:Granulocytes / Q000166:cytology / Q000502:physiology*; D006801:Humans; D019041:L-Selectin / Q000378:metabolism; D007781:Lactoferrin / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D039481:CD11b Antigen; D017077:Culture Media, Conditioned; D019041:L-Selectin; D007781:Lactoferrin