{"doi":"10.1165/rcmb.2011-0260oc","title":"Role of CXCL5 in Leukocyte Recruitment to the Lungs during Secondhand Smoke Exposure","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality in the United States. The major cause of COPD is cigarette smoking. Extensive leukocyte influx into the lungs, mediated by chemokines, is a critical event leading to COPD. Although both resident and myeloid cells secrete chemokines in response to inflammatory stimuli, little is known about the role of epithelial-derived chemokines, such as CXC chemokine ligand (CXCL)5, in the pathogenesis of cigarette smoke–induced inflammation. To explore the role of CXCL5, we generated CXCL5 gene–deficient mice and exposed them to secondhand smoke (SHS) for 5 hours/day for 5 days/week up to 3 weeks (subacute exposure). We observed a reduced recruitment of leukocytes to the lungs of CXCL5−/− mice compared with their wild-type (WT) counterparts, and noted that macrophages comprised the predominant leukocytes recruited to the lungs. Irradiation experiments performed on CXCL5−/− or WT mice transplanted with WT or CXCL5−/− bone marrow revealed that resident but not hematopoietic cell–driven CXCL5 is important for mediating SHS-induced lung inflammation. Interestingly, we observed a significant reduction of monocyte chemotactic protein–1 (MCP-1/CC chemokine ligand 2) concentrations in the lungs of CXCL5−/− mice. The instillation of recombinant MCP-1 in CXCL5−/− mice reversed macrophage recruitment. Our results also show the reduced activation of NF-κB/p65 in the lungs, as well as the attenuated activation of C-Jun N-terminal kinase, p42/44, and p38 mitogen-activated protein kinases and the expression of intercellular adhesion molecule-1 in the lungs of SHS-exposed CXCL5−/− mice. Our findings suggest an important role for CXCL5 in augmenting leukocyte recruitment in SHS-induced lung inflammation, and provide novel insights into CXCL5-driven pathogenesis.</jats:p>","journal":"American Journal of Respiratory Cell and Molecular Biology","year":2012,"id":606258,"datarank":0.6284482113039639,"base_score":4.189654742026425,"endowment":4.189654742026425,"self_citation_contribution":0.6284482113039639,"citation_network_contribution":0.0,"self_endowment_contribution":0.6284482113039639,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":65,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1093224,"name":"Sanjay Batra","orcid":"0000-0002-7425-0761","position":1,"is_corresponding":false},{"id":761015,"name":"Shanshan Cai","orcid":"0000-0003-0117-5171","position":2,"is_corresponding":false},{"id":1556227,"name":"Junjie Mei","orcid":null,"position":3,"is_corresponding":false},{"id":260645,"name":"G. Scott Worthen","orcid":"0000-0002-9073-2242","position":4,"is_corresponding":false},{"id":1556236,"name":"Arthur L. Penn","orcid":null,"position":5,"is_corresponding":false},{"id":451665,"name":"Samithamby Jeyaseelan","orcid":"0000-0002-1959-1328","position":6,"is_corresponding":false},{"id":969195,"name":"Gayathriy Balamayooran","orcid":"0000-0003-2677-789X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Role of CXCL5 in Leukocyte Recruitment to the Lungs during Secondhand Smoke Exposure","abstract":"<jats:title>Abstract</jats:title>\n                  <jats:p>Chronic obstructive pulmonary disease (COPD) is the third leading cause of mortality in the United States. The major cause of COPD is cigarette smoking. Extensive leukocyte influx into the lungs, mediated by chemokines, is a critical event leading to COPD. Although both resident and myeloid cells secrete chemokines in response to inflammatory stimuli, little is known about the role of epithelial-derived chemokines, such as CXC chemokine ligand (CXCL)5, in the pathogenesis of cigarette smoke–induced inflammation. To explore the role of CXCL5, we generated CXCL5 gene–deficient mice and exposed them to secondhand smoke (SHS) for 5 hours/day for 5 days/week up to 3 weeks (subacute exposure). We observed a reduced recruitment of leukocytes to the lungs of CXCL5−/− mice compared with their wild-type (WT) counterparts, and noted that macrophages comprised the predominant leukocytes recruited to the lungs. Irradiation experiments performed on CXCL5−/− or WT mice transplanted with WT or CXCL5−/− bone marrow revealed that resident but not hematopoietic cell–driven CXCL5 is important for mediating SHS-induced lung inflammation. Interestingly, we observed a significant reduction of monocyte chemotactic protein–1 (MCP-1/CC chemokine ligand 2) concentrations in the lungs of CXCL5−/− mice. The instillation of recombinant MCP-1 in CXCL5−/− mice reversed macrophage recruitment. Our results also show the reduced activation of NF-κB/p65 in the lungs, as well as the attenuated activation of C-Jun N-terminal kinase, p42/44, and p38 mitogen-activated protein kinases and the expression of intercellular adhesion molecule-1 in the lungs of SHS-exposed CXCL5−/− mice. Our findings suggest an important role for CXCL5 in augmenting leukocyte recruitment in SHS-induced lung inflammation, and provide novel insights into CXCL5-driven pathogenesis.</jats:p>","is_dataset_classified":null,"base_score":4.189654742026425,"endowment":4.189654742026425,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22362385","pmcid":"PMC3402800","openalex_id":"https://openalex.org/W2098809388","authors":[],"funders":[{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL-091958","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI099479","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL091958","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL105834","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL-091958S1","title":null}],"total_grants":5,"fwci":1.9068,"citation_percentile":0.86778675,"influential_citations":0,"citation_trend":[{"year":2013,"count":5},{"year":2014,"count":2},{"year":2015,"count":1},{"year":2016,"count":7},{"year":2017,"count":3},{"year":2018,"count":4},{"year":2019,"count":5},{"year":2020,"count":7},{"year":2021,"count":1},{"year":2022,"count":5},{"year":2023,"count":9},{"year":2024,"count":14},{"year":2025,"count":1},{"year":2026,"count":1}],"oa_status":"green","license":"https://academic.oup.com/pages/standard-publication-reuse-rights","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3402800","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3402800","host_type":"repository"},{"url":"https://academic.oup.com/ajrcmb/article-pdf/47/1/104/66897115/ajrcmb_47_1_104.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1165/rcmb.2011-0260oc","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22362385","host_type":"repository"},{"url":"https://digitalcommons.lsu.edu/vetmed_pubs/1071","host_type":"journal"},{"url":"https://digitalcommons.lsu.edu/vetmed_pubs/1378","host_type":"journal"},{"url":"http://europepmc.org/articles/PMC3402800","host_type":"repository"},{"url":"https://repository.lsu.edu/vetmed_pubs/1071","host_type":"journal"}],"fields_of_study":["Chronic Obstructive Pulmonary Disease (COPD) Research","Pediatric health and respiratory diseases","Immune Response and Inflammation","Animals","Bone Marrow Cells","Chemokine CCL2","Chemokine CXCL5","Cyclin-Dependent Kinases","Environmental Exposure","Female","Inflammation","Intercellular Adhesion Molecule-1","JNK Mitogen-Activated Protein Kinases","Leukocytes","Lung","Macrophages","Mice","Mice, Inbred C57BL","Mice, Knockout","Peptide Fragments","Pulmonary Disease, Chronic Obstructive","Tobacco Smoke Pollution","Transcription Factor RelA","Transcription Factors","Tumor Suppressor Protein p53","p38 Mitogen-Activated Protein Kinases","Cyclin-Dependent Kinase-Activating Kinase"],"mesh_terms":["Cyclin-Dependent Kinase-Activating Kinase","Animals","Bone Marrow Cells","Environmental Exposure","Female","Inflammation","Leukocytes","Lung","Macrophages","Mice, Inbred C57BL","Peptide Fragments","Tobacco Smoke Pollution","Transcription Factors","Tumor Suppressor Protein p53","Mice, Knockout","Intercellular Adhesion Molecule-1","Cyclin-Dependent Kinases","Chemokine CCL2","Pulmonary Disease, Chronic Obstructive","JNK Mitogen-Activated Protein Kinases","p38 Mitogen-Activated Protein Kinases","Mice","Transcription Factor RelA","Chemokine CXCL5"],"keywords":["CXCL5","Chemokine","COPD","Inflammation","Immunology","Medicine","Chemokine receptor","Lung","Internal medicine"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-30T04:10:49.637751Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}