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Leukocyte Disorders: Quantitative and Qualitative Disorders of the Neutrophil, Part 1

Laurence A. Boxer MD1
R. Alexander Blackwood MD, PhD2
 1 Professor and Director, Pediatric Hematology/Oncology, University of Michigan, Ann Arbor, MI. Dr Boxer participated in Amgen Corporation's phase III trial evaluating the efficacy of rhG-CSF in the treatment of patients who have severe congenital neutropenia. He also participated in Genentech's trial evaluating the efficacy of gamma-interferon in the treatment of patients who have chronic granulomatous disease
2 Assistant Professor of Pediatrics and Communicable Diseases, Division of Pediatric Infectious Diseases, University of Michigan, Ann Arbor, MI.

Introduction

Neutrophils form the first line of defense against most bacterial and fungal pathogens after disruption of the skin and mucous membranes. Once tissue is invaded by microorganisms, a variety of vasoactive and chemotactic mediators are released by the involved tissue. In response to these chemotactic peptides, neutrophils, normally found in the circulation, adhere to the inflamed endothelium and migrate to the site of infection where the phagocytes ingest and kill the invading microorganisms. Neutrophils also release a variety of cytokines that may modify the neutrophils' own responses as well as interact with other elements of the immune system. Neutrophils, therefore, are both important effectors and regulators of the host defense system. Because of the complexity of this defense system and the major role played by neutrophils, both primary and acquired defects in neutrophil number or function result in persistent as well as recurrent infections.

Primary defects in neutrophil number or function are relatively rare, but they must be considered in a child who presents with recurrent infections. Early identification and management of affected children lead to decreased morbidity and mortality. Although care predominantly has been supportive in the past through the use of prophylactic and therapeutic antibiotics, specific therapies now are becoming available to reduce the frequency of infections in some diseases.




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