Increased bronchoalveolar lavage human beta-defensin type 2 in bronchiolitis obliterans syndrome after lung transplantation.
Human beta-defensin-2 (HBD)2 is an antimicrobial peptide that participates in the innate host immune defense. HBD2 is present in bronchoalveolar lavage (BAL) fluid during conditions associated with airway inflammation but not in normal subjects. We measured HBD2 concentrations by semiquantitative Western analysis in BAL of prelung transplant patients (PRE) and postlung-transplant BAL associated with either "quiescent" histopathology (i.e., without acute cellular rejection or infection) (NORMAL POST) or with bronchiolitis obliterans syndrome (BOS). HBD2 levels were not different for PRE (n=9) versus NORMAL POST-transplant BAL specimens (n=22) (204+/-180 vs. 82+/-60 pg/mL; P=NS). The BAL HBD2 concentrations were significantly elevated, however, with BOS (n=8) (1,270+/-430 pg/mL; P<0.001). HBD2 has been previously shown to elicit an adaptive immune response by means of recruitment of immature CD34 dendritic cells and memory (CD4/CD45RO) T lymphocytes through interactions with their chemokine receptor, CCR6. Furthermore, HBD2 with CD14 in human tracheobronchial epithelium can complex with "toll-like receptors" to activate the nuclear factor (NF)-kappaB pathway and therefore promote cytokine gene expression. We therefore speculate that complex interactions between adaptive and innate immunity may contribute to the propagation of airway inflammation in BOS.
Ross
David J
DJ
Division of Pulmonary and Critical-Care Medicine and the Will Rogers Institute for Pulmonary Research, David Geffen School of Medicine; U.C.L.A. Medical Center, Los Angeles, CA 90095-1690, USA. dross@mednet.ucla.edu
Cole
Alexander M
AM
Yoshioka
Dawn
D
Park
Albert K
AK
Belperio
John A
JA
Laks
Hillel
H
Strieter
Robert M
RM
Lynch
Joseph P
JP
Kubak
Bernard
B
Ardehali
Abbas
A
Ganz
Tomas
T
D001989:Bronchiolitis Obliterans / Q000378:metabolism* / Q000601:surgery*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D006801:Humans; D016040:Lung Transplantation; D009994:Osmolar Concentration; D011184:Postoperative Period; D011300:Preoperative Care; D023083:beta-Defensins / Q000378:metabolism*
C106641:DEFB4A protein, human; D023083:beta-Defensins