STRUCTURAL RESPONSES OF PULMONARY INTRAVASCULAR MACROPHAGES IN LENTIVIRUS-INFECTED AND OR RECOMBINANT OVINE INTERFERON-TAU-TREATED LAMBS/

Ovine lentivirus (OvLV), a retrovirus, infects and disseminates to var ious tissue organs via monocytes. The differentiation of infected mono cytes into macrophages is a prerequisite for viral replication, and th e presence of infected macrophages in tissue organs induces chronic im munopathology such as lymphoid interstitial pneumonia. The pulmonary i ntravascular macrophage (PIM) is a recently identified mononuclear pha gocyte in domestic animal species, including sheep. Recombinant ovine interferon-tau (roIFN-tau), a type I IFN originally named as the ovine trophoblast protein, has potent antiviral activity against OvLV and h uman immunodeficiency virus and prevents the development of OvLV-assoc iated lung pathology. We investigated and compared the structural feat ures of PIMs in OvLV-infected and/or roIFN-tau-treated 1-month-old lam bs using transmission electron microscopy. The PIMs' numerical counts were performed in toluidine blue-stained sections of Epoxy-embedded lu ng tissues. A reduction in the number of PIMs was observed with OvLV i nfection and/or roIFN-tau treatment of lambs as compared to the contro l group (P less than or equal to 0.05). The majority of the PIMs in Ov LV-infected and/or roIFN-tau-treated groups Mere devoid of their surfa ce coat. The PIMs of OvLV-infected lambs exhibited signs of biosynthet ic activation such as expanded rough endoplasmic reticulum, prominent Golgi complexes, and accumulation of secretory vesicles. A few PIMs co ntained OvLV-like structures. In roIFN-tau-treated OvLV-infected lambs : the lymphocytes had ruffled plasma membranes and were in intimate co ntact with the PIMs, as is observed during cytotoxic cell-mediated kil ling of target; cells. Most of the PIMs in roIFN-tau-treated OvLV-infe cted lambs appeared smaller in size. Ovine lentivirus and roIFN-tau, i ndividually or in combination, alter the integrity of the surface coat of PIMs and cause their disappearance from the lungs. Ovine lentiviru s infection induces morphological changes that correlate with cytotoxi c cell behavior between lymphocytes and PIMs in roIFN-tau-treated or p lacebo-treated lambs. The loss of PIMs, probably infected with OvLV, e ither through direct killing by roIFN-tau or indirectly by roIFN-tau-a ctivated cytotoxic T lymphocytes may represent different aspects of th erapeutic actions of this cytokine. Anat. Rec. 251.472-485, 1998. (C) 1998 Wiley-Liss, Inc.