Hyaline membrane disease is the most common type of acute lung injury in the newborn period. Surfactant deficiency or impaired function has been shown to be an important component in its pathogenesis. If normal healing does not occur in the first week of life, a chronic state of injury and continuing repair occurs (bronchopulmonary dysplasia, BPD). Two mannose- specific homologous lectins have been localized to the lung. Type II cells synthesize and secrete surfactant-associated protein A (SP-A). Proposed functions for SP-A include phospholipid clearance and recycling, opsonization of bacteria, and complement fixation. Alveolar macrophages (Mphi) synthesize and express on their surface a mannose-specific endocytic receptor (MR). The MR is involved in clearance of extracellular enzymes and pathogens and has been suggested to be involved in recognition and uptake of SP-A/bacterial complexes by Mphi. Three additional surfactant associated proteins have been identified: SP-B, SP-C, and SP-D. SP-B and SP-C promote rapid surface absorption of phospholipids, and are suggested to be involved in recycling of surfactant lipid. There is evidence that SP-D is also a pulmonary lectin. Using an extensive library of normal human fetal lungs and of lungs and other tissues of newborn infants with acute lung injury (HMD), those with normal repair and those with abnormal repair (BPD), we will use immunohistochemistry to localize SP-A, SP-B and SP-C precursor and correlate our findings with the stage of lung development, the presence of lung injury and the stage of lung repair. Using in situ hybridization techniques, we will localize the mRNA for each of these proteins. In addition, we will correlate the expression of mRNA with the stage of lung development, the presence of lung injury, and the stage of lung repair. We will determine whether cells in tracheobronchial glands and conducting airway epithelia which are immunohistochemically stained for SP-A express mRNA for SP-A by in situ hybridization studies. We will use transgenic mice that carry a chimeric gene consisting of the 5' flanking sequences of the human SP-C gene linked to the chloramphenicol acetyl transferase gene to study the cellular localization, tissue distribution and ontogeny of SP-C gene expression and its control elements. Using isolated rat alveolar macrophages, we will examine the role of the MR in recognition and clearance of SP-A and SP-A/lipid complexes. Using isolated rat alveolar macrophages we will look at the ability of SP-A to enhance bacterial clearance, to determine if ingestion is receptor- mediated, and to begin initial characterization/identification of the receptor involved, test for mannan inhibitable processes and determine if the mannose receptor is involved.
| Chroneos, Z C; Abdolrasulnia, R; Whitsett, J A et al. (1996) Purification of a cell-surface receptor for surfactant protein A. J Biol Chem 271:16375-83 |
| Watanabe, T; Oki, Y; Orth, D N (1989) Kinetic actions and interactions of arginine vasopressin, angiotensin-II, and oxytocin on adrenocorticotropin secretion by rat anterior pituitary cells in the microperifusion system. Endocrinology 125:1921-31 |
