PMID- 22227380
OWN - NLM
STAT- MEDLINE
DCOM- 20120601
LR  - 20220330
IS  - 1535-4970 (Electronic)
IS  - 1073-449X (Linking)
VI  - 185
IP  - 8
DP  - 2012 Apr 15
TI  - An association between neutrophils and immunoglobulin free light chains in the 
      pathogenesis of chronic obstructive pulmonary disease.
PG  - 817-24
LID - 10.1164/rccm.201104-0761OC [doi]
AB  - RATIONALE: Neutrophils are key players in chronic obstructive pulmonary disease 
      (COPD), and increased numbers of neutrophils are present in sputum and lung 
      tissue of patients with COPD. Interestingly, immunoglobulin free light chains 
      (IgLC) are able to prolong the life of neutrophils; therefore, IgLC may 
      contribute to the chronic state of inflammation. OBJECTIVES: In this study, the 
      relation between IgLC and COPD has been investigated. METHODS: We investigated 
      the presence of IgLC in different murine lung emphysema models. IgLC levels in 
      serum from mice and patients with COPD were examined by Western blot analysis and 
      ELISA, respectively. IgLC levels in lung tissue were determined by 
      immunohistochemistry. Fluorescence-activated cell sorter and immunofluorescent 
      analysis were used to detect binding between IgLC and human neutrophils. 
      Interleukin-8 (CXCL8) release by neutrophils after IgLC incubation was measured 
      by ELISA. The effect of F991, an IgLC antagonist, was examined on the neutrophil 
      influx in murine lungs after 5 days of smoke exposure. MEASUREMENTS AND MAIN 
      RESULTS: Increased levels of IgLC in serum of cigarette smoke-exposed and 
      cigarette smoke extract-treated mice compared with control mice were observed. 
      Patients with COPD showed increased serum IgLC and expression of IgLC in lung 
      tissue compared with healthy volunteers. Interestingly, IgLC bound to neutrophils 
      and activated neutrophils to release CXCL8. F991 inhibited the IgLC binding to 
      neutrophils and reduced the smoke-induced neutrophil influx in murine lungs after 
      smoke exposure. CONCLUSIONS: This study describes for the first time an 
      association between neutrophils and IgLC in the pathophysiology of COPD, which 
      could open new avenues to targeted treatment of this chronic disease.
FAU - Braber, Saskia
AU  - Braber S
AD  - Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty 
      of Science, Utrecht University, The Netherlands. s.braber@uu.nl
FAU - Thio, Marco
AU  - Thio M
FAU - Blokhuis, Bart R
AU  - Blokhuis BR
FAU - Henricks, Paul A J
AU  - Henricks PA
FAU - Koelink, Pim J
AU  - Koelink PJ
FAU - Groot Kormelink, Tom
AU  - Groot Kormelink T
FAU - Bezemer, Gillina F G
AU  - Bezemer GF
FAU - Kerstjens, Huib A M
AU  - Kerstjens HA
FAU - Postma, Dirkje S
AU  - Postma DS
FAU - Garssen, Johan
AU  - Garssen J
FAU - Kraneveld, Aletta D
AU  - Kraneveld AD
FAU - Redegeld, Frank A
AU  - Redegeld FA
FAU - Folkerts, Gert
AU  - Folkerts G
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20120106
PL  - United States
TA  - Am J Respir Crit Care Med
JT  - American journal of respiratory and critical care medicine
JID - 9421642
RN  - 0 (Biomarkers)
RN  - 0 (Immunoglobulin Light Chains)
RN  - 0 (Smoke)
SB  - IM
CIN - Am J Respir Crit Care Med. 2012 Apr 15;185(8):793-5. PMID: 22505747
MH  - Aged
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Bronchoalveolar Lavage Fluid/chemistry/cytology
MH  - Disease Models, Animal
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - Immunoglobulin Light Chains/*metabolism
MH  - Leukocyte Count
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Neutrophil Activation
MH  - Neutrophils/drug effects/*metabolism
MH  - Pulmonary Disease, Chronic Obstructive/*physiopathology
MH  - Random Allocation
MH  - Sampling Studies
MH  - Smoke/adverse effects
MH  - Smoking/*adverse effects
EDAT- 2012/01/10 06:00
MHDA- 2012/06/02 06:00
CRDT- 2012/01/10 06:00
PHST- 2012/01/10 06:00 [entrez]
PHST- 2012/01/10 06:00 [pubmed]
PHST- 2012/06/02 06:00 [medline]
AID - rccm.201104-0761OC [pii]
AID - 10.1164/rccm.201104-0761OC [doi]
PST - ppublish
SO  - Am J Respir Crit Care Med. 2012 Apr 15;185(8):817-24. doi: 
      10.1164/rccm.201104-0761OC. Epub 2012 Jan 6.