Biomedical subjects

Vedang A Londhe

Publications and source records attributed to Vedang A Londhe.

3 recordsLinked to original sources

PubMed2006

Developmental pathways and specification of intrapulmonary stem cells.

Tissues have the capacity to maintain a homeostatic balance between wear-and-tear and regeneration. Repair of non-lethal injury also activates cell proliferation to repopulate the injured sites with appropriate cell types and to restore function. Although controversial, the source of the material appears to be at least partly from pools of unique, multipotent stem cells that reside in specialized locations referred to as "niches." Molecular interactions between the niche and the intracellular factors within stem cells are crucial in maintaining stem cell functions, particularly the balance between self-renewal and differentiation. Many of the mediators of the stem cell-niche interactions are similar or identical to those that control developmental pathways during organogenesis. In this review, we present a systematic discussion and evaluation of the relevant literature with a focused emphasis on three primary signaling pathways, WNT, SHH and BMP with potentially overlapping roles during both development and stem cell maintenance.

Humans↗

PubMed2005

CXCR2/CXCR2 ligand biological axis impairs alveologenesis during dsRNA-induced lung inflammation in mice.

The histologic phenotype of bronchopulmonary dysplasia (BPD) is characterized by decreased alveolization and is preceded by infiltration of activated neutrophils into the lung that can lead to sustained lung injury and potential interruption of normal lung development. Potential pathogens triggering early neutrophil influx include either prenatal or postnatal exposure to bacteria or viruses. Specific mechanisms recruiting neutrophils to the lung and subsequently decreasing alveolization during virus-induced lung inflammation and injury have not been fully elucidated. Because CXC chemokines, such as CXCL1 and CXCL2/3 acting through their putative receptor, CXCR2, are potent neutrophil chemoattractants, the authors investigated their role in dsRNA-induced lung injury and decreased alveolization, in which dsRNA (poly IC) is a well-described synthetic agent mimicking acute viral infection. Intratracheal dsRNA led to significant increases in neutrophil infiltration and lung injury at 72 hours and to decreased alveolization at 5 days after dsRNA exposure in newborn (10 days old) BALB/c mice, when compared with controls treated and not treated with ssRNA (poly C). Expression of CXCL1 and CXCR2 paralleled neutrophil recruitment to the lung and preceded the decrease in alveolization. Inhibition of CXCR2/CXCR2 ligand interaction by pretreating dsRNA-exposed mice with an anti-CXCR2 neutralizing antibody significantly attenuated neutrophil sequestration and lung injury, and preserved normal alveolization. These findings demonstrate that the CXCR2/CXCR2 ligand biologic axis plays an important role during the pathogenesis of dsRNA-induced lung injury and decreased alveolization and may be relevant to the pathogenesis of BPD.

Animals↗

PubMed2005

CXCR2 is critical for dsRNA-induced lung injury: relevance to viral lung infection.

BACKGROUND: Respiratory viral infections are characterized by the infiltration of leukocytes, including activated neutrophils into the lung that can lead to sustained lung injury and potentially contribute to chronic lung disease. Specific mechanisms recruiting neutrophils to the lung during virus-induced lung inflammation and injury have not been fully elucidated. Since CXCL1 and CXCL2/3, acting through CXCR2, are potent neutrophil chemoattractants, we investigated their role in dsRNA-induced lung injury, where dsRNA (Poly IC) is a well-described synthetic agent mimicking acute viral infection. METHODS: We used 6-8 week old female BALB/c mice to intratracheally inject either single-stranded (ssRNA) or double-stranded RNA (dsRNA) into the airways. The lungs were then harvested at designated timepoints to characterize the elicited chemokine response and resultant lung injury following dsRNA exposure as demonstrated qualititatively by histopathologic analysis, and quantitatively by FACS, protein, and mRNA analysis of BAL fluid and tissue samples. We then repeated the experiments by first pretreating mice with an anti-PMN or corresponding control antibody, and then subsequently pretreating a separate cohort of mice with an anti-CXCR2 or corresponding control antibody prior to dsRNA exposure. RESULTS: Intratracheal dsRNA led to significant increases in neutrophil infiltration and lung injury in BALB/c mice at 72 h following dsRNA, but not in response to ssRNA (Poly C; control) treatment. Expression of CXCR2 ligands and CXCR2 paralleled neutrophil recruitment to the lung. Neutrophil depletion studies significantly reduced neutrophil infiltration and lung injury in response to dsRNA when mice were pretreated with an anti-PMN monoclonal Ab. Furthermore, inhibition of CXCR2 ligands/CXCR2 interaction by pretreating dsRNA-exposed mice with an anti-CXCR2 neutralizing Ab also significantly attenuated neutrophil sequestration and lung injury. CONCLUSION: These findings demonstrate that CXC chemokine ligand/CXCR2 biological axis is critical during the pathogenesis of dsRNA-induced lung injury relevant to acute viral infections.

Journal Article↗