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Published online before print December 6, 2004

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(Journal of Leukocyte Biology. 2005;77:439-443.)
© 2005 by Society for Leukocyte Biology

Neutrophils and keratinocytes in innate immunity—cooperative actions to provide antimicrobial defense at the right time and place

Niels Borregaard^*,1, Kim Theilgaard-Mönch^*, Jack B. Cowland^*, Mona Ståhle and Ole E. Sørensen^*

^* The Granulocyte Research Laboratory, Department of Hematology, Rigshospitalet, University of Copenhagen, Denmark; and
Department of Dermatology, Karolinska Institutet, Stockholm, Sweden

¹Correspondence: The Granulocyte Research Laboratory, Department of Hematology, Rigshospitalet-4042, 9 Blegdamsvej, DK-2100, University of Copenhagen, Copenhagen, Denmark. E-mail: borregaard{at}rh.dk

The human neutrophil is a professional phagocyte of fundamental importance for defense against microorganisms, as witnessed by the life-threatening infections occurring in patients with neutropenia or with defects that result in decreased microbicidal activity of the neutrophil [¹ , ² ]. Likewise, the skin and mucosal surfaces provide important barriers against infections. Traditionally, these major defense systems, the epithelial cells and the neutrophils, have been viewed as limited in their armory: The epithelial cells provide defense by constituting a physical barrier, and the neutrophils provide instant delivery of preformed antimicrobial substances or on-the-spot assembly of the multicomponent reduced nicotinamide adenine dinucleotide phosphate oxidase from stored components for the generation of reactive oxygen metabolites. Recent research has shown that epithelial cells are highly dynamic and able to generate antimicrobial peptides in response not only to microbial infection itself [^{3 4 5 6} ] but more importantly, to the growth factors that are called into play when the physical barrier is broken, and the risk of microbial infection is imminent [⁷ ]. Likewise, the neutrophil changes its profile of actively transcribed genes when it diapedeses into wounded skin [⁸ ]. This results in generation of signaling molecules, some of which support the growth and antimicrobial potential of keratinocytes and epithelial cells. This paper will highlight some recent advances in this field.

Key Words: hCAP-18 • NGAL • antibiotic peptides

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