Chemokine redundancy in BOS pathogenesis. A possible role also for the CC chemokines: MIP3-beta, MIP3-alpha, MDC and their specific receptors.
Bronchiolitis obliterans syndrome (BOS) is one of the most important factors limiting the long-term survival of lung transplant recipients (LTR), however its pathogenesis still remains unclear. We hypothesized that an increased production of certain specific proinflammatory mediators in the first post-transplant year would predispose to BOS. We retrospectively evaluated temporal kinetics of some CC chemokines that have not yet been evaluated, including CCL3/MIP1-alpha, CCL4/MIP1-beta, CCL17/TARC, CCL19/MIP3-beta, CCL20/MIP3-alpha, CCL22/MDC and CCL26/eotaxin, in broncho-alveolar lavage fluid (BAL-f) in the first post-transplant year in a cohort of 8 LTR before the development of BOS (pre-BOS LTR) and 8 LTR with long-term stable clinical conditions (stable LTR). Chemokine levels were assayed by means of a multiplex sandwich ELISA. Furthermore, for those ligands which resulted significantly predictive of BOS onset, we analyzed the expression of specific receptors (CCR) on BAL cells. The proportion of CCR-expressing BAL cells was assessed by flow cytometry. We demonstrated that MIP3-beta/CCL19, MIP3-alpha/CCL20, MDC/CCL22 levels at 6 months post-transplant significantly predicted BOS onset. In addition, the temporal behavior of these factors resulted significantly different in pre-BOS patients as compared to stable LTR. Finally the expression of CCR was documented on BAL lymphocytes and macrophages, and, in some cases, their expression was found to vary between the two groups. Within the complexity of the chemokine network, these three CCL factors could play an additive role in the pathogenesis of the inflammatory process leading to bronchiolar fibro-obliteration.
Meloni
F
F
Department of Haematological Pneumological and Cardiovascular Sciences, Section of Pneumology, University of Pavia & Foundation IRCCS San Matteo, Pavia, Italy. f.meloni@smatteo.pv.it
Solari
N
N
Miserere
S
S
Morosini
M
M
Cascina
A
A
Klersy
C
C
Arbustini
E
E
Pellegrini
C
C
Viganò
M
M
Fietta
A M
AM
D051722:ADAM Proteins / Q000032:analysis / Q000276:immunology; D000328:Adult; D001989:Bronchiolitis Obliterans / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D054415:Chemokine CCL19 / Q000032:analysis* / Q000276:immunology; D054418:Chemokine CCL20 / Q000032:analysis* / Q000276:immunology; D005260:Female; D006801:Humans; D016040:Lung Transplantation / Q000276:immunology*; D019402:Macrophage Inflammatory Proteins / Q000032:analysis* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D019707:Receptors, Chemokine / Q000032:analysis* / Q000276:immunology; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000276:immunology
C108355:CCL20 protein, human; D054415:Chemokine CCL19; D054418:Chemokine CCL20; D019402:Macrophage Inflammatory Proteins; D019707:Receptors, Chemokine; D025521:Tumor Suppressor Proteins; D051722:ADAM Proteins; C090222:ADAM11 protein, human