Gerami D. Seitzman

Lung lymphocyte elimination by apoptosis in the murine response to intratracheal particulate antigen.

Pulmonary immune responses are suited to determine mechanisms of lymphocyte elimination, as lung inflammation must be regulated tightly to preserve gas exchange. The self-terminating response of primed C57BL/6 mice to intratracheal challenge with the T cell-dependent Ag sheep erythrocytes (SRBC) was used to test the importance of lung lymphocyte apoptosis in pulmonary immunoregulation. Apoptosis of alveolar and interstitial lymphocytes was demonstrated morphologically, by three independent methods to detect DNA fragmentation, and by surface expression of phosphatidylserine. Apoptotic lymphocytes were exclusively CD4-, CD8-, B220-, but many were CD3+ and Thy 1+. Inhibiting apoptosis by in vivo cyclosporine treatment prolonged lung lymphocyte accumulation following SRBC challenge. Experiments using mice homozygous for the lpr or gld mutations showed that pulmonary lymphocyte apoptosis depended on expression of Fas (CD95) and its ligand (Fas-L). Pulmonary inflammation increased on repeated intratracheal SRBC challenge of lpr/lpr mice, in contrast to the waning response in normal mice. These results confirm that in situ lymphocyte apoptosis contributes to termination of immune responses in nonlymphoid organs, probably because of activation-induced cell death, and may be important in inducing tolerance to repeated antigen exposure.

Repeated Intratracheal Challenge with Particulate Antigen Modulates Murine Lung Cytokines

When lungs of experimental animals are repeatedly challenged with Ag, pulmonary inflammation wanes via unknown mechanisms. We hypothesized that changes in the balance of lung cytokines are responsible for immune down-regulation to repeated Ag challenge. We used intratracheal (IT) challenge of primed C57BL/6 mice with SRBC and on various days after single (1IT) or triple (3IT) challenge counted lung inflammatory cells and measured whole-lung cytokine mRNA and protein concentrations using RT-PCR and ELISA. We found that lung lymphocyte numbers and parenchymal lung inflammation decreased significantly at days 6 and 9 after final Ag challenge in 3IT mice compared with 1IT mice. Lungs of 3IT mice showed the following changes in relative mRNA expression: an earlier peak in IL-10, decreased IL-1β, and a change from a Th2 response in 1IT mice to a Th1 response in 3IT mice (with pronounced increases in IL-12, IL-18, and IFN-γ and decreased IL-4, IL-13, and IL-5). Similar types of changes were seen in whole-lung protein concentrations for TNF-α, IL-10, IL-12 p40, IFN-γ, and IL-4. Additionally, mRNA expression of the endothelial selectins CD62E and CD62P decreased and lung lymphocyte apoptosis increased in the 3IT group. Thus, physiologic down-regulation of the pulmonary immune response to repeated Ag exposure is characterized by increased anti- and decreased proinflammatory cytokines that accompanies Th1 polarization. Similar mechanisms may act to minimize chronic lung inflammation in the majority of normal humans who do not develop progressive lung pathology when repeatedly exposed to inhaled or aspirated environmental Ags.

Lymphocyte-endothelial cell adhesive interactions in lung immunity: lessons from the murine response to particulate antigen.

The adhesive interaction between lymphocytes and lung endothelial cells presents an attractive arena for the development of novel therapeutic agents to modify pathologic pulmonary immune responses. The conceptual basis for choosing molecular targets to modulate this adhesive interaction derives, in large part, from results of murine experimental model systems of the pulmonary immune response. This article reviews one such model, the response of primed C57BL/6 mice to the particulate antigen sheep erythrocytes. Novel data are presented on the effect of a blocking anti-alpha(4) integrin monoclonal antibody on lung leukocyte and lymphocyte subset accumulation after intratracheal (IT) antigen challenge. Results from this model system have indicated that lymphocytes may use either the endothelial selectins or alpha(4) integrin as independent pathways to initiate recruitment into the lungs.

Bilateral surgically induced necrotising scleritis with secondary superinfection

Surgically induced necrotising scleritis (SINS) is a rare complication of ocular surgery that has been described after pterygium excision, cataract extraction, trabeculectomy, penetrating keratoplasty, strabismus surgery, and retinal detachment repair.1–3 We describe a rare case of bilateral necrotising scleritis complicated by a secondary polymicrobial infection following uncomplicated phacoemulsification and pterygia excision. A 66 year old Samoan male, with type II diabetes, end stage renal disease, coronary artery disease, and gout underwent uncomplicated combined phacoemulsification and bare sclera pterygium excision (without antimetabolites) in the right eye, followed 1 month later by the same combined procedure in the left eye. Three weeks later, the patient developed severe right sided eye pain. An erythrocyte sedimentation rate was 98 mm in the first hour, and oral prednisone (80 mg/day) was initiated. A temporal …

Treatment of neurotrophic keratopathy with nasal dilator strips

Neurotrophic keratopathy, characterised by poorly healing corneal epithelium, occurs in eyes with decreased corneal sensory innervation. Clinical findings include chronic epithelial defects and corneal ulceration. Numerous conditions predispose to neurotrophic keratopathy including diabetes mellitus, accidental and surgical trauma, herpes simplex and herpes zoster keratitis, leprosy, and topical anaesthetic abuse. Management of neurotrophic keratopathy includes ocular lubrication, pressure patching, autologous serum eye drops,1 fitting of a bandage contact lens,2 amniotic membrane grafting,3,4 and surgical tarsorrhaphy. Surgical tarsorrhaphy can be very successful in resolving neurotrophic corneal ulceration,5 but many patients find this option cosmetically unacceptable. We describe a novel method of …

Isolated unilateral congenital lacrimal gland agenesis presenting as filamentary keratopathy in a child.

Congenital lacrimal gland agenesis is extremely rare, and there are only a few cases reported in the literature. These cases involve bilateral lacrimal gland agenesis associated, in some instances, with salivary gland agenesis and abnormalities of the lacrimal puncta and canaliculi. This report, to our knowledge, presents the first documented case of unilateral lacrimal gland agenesis, resulting in unilateral filamentary keratopathy.

Steel wool keratopathy: a clinical sign of chronic inflammation.

Purpose: To introduce into the clinical nomenclature a sign frequently observed in our patients with persistent corneal inflammation associated with herpetic stromal keratitis. Methods: Case reports and review of the literature. Results: Four representative patients with herpesvirus stromal keratitis are presented. Herpes simplex virus-1 (HSV-1) was confirmed by culture in 1 case and by polymerase chain reaction in a second case. In the remaining 2 cases, the diagnosis was made based on characteristic clinical findings for herpes simplex virus and varicella zoster virus (VZV). On clinical examination, all 4 representative cases of stromal keratitis revealed a well-defined, localized region of intertwined, metallic-like, polychromatic material in the corneal stroma, a sign we have termed steel wool keratopathy. We have only rarely observed this finding in patients with stromal keratitis not caused by a herpesvirus. Conclusion: Steel wool keratopathy seems to represent a focal region of stromal degeneration or deposition associated with chronic inflammation. Although we most often observe this finding in patients with stromal keratitis secondary to HSV or VZV, we cannot exclude the possibility that this sign represents the sequelae of chronic/recurrent inflammation rather than a specific pathologic response to herpetic antigens.

Unilateral posterior stromal keratitis possibly secondary to Lyme disease.

Purpose: To report a case of Lyme disease presenting as unilateral posterior stromal keratitis in a pediatric patient. Methods: Case report and review of available literature. Results: A 13-year-old adolescent with unilateral painless blurry vision presented with prominent posterior corneal stromal haze. A positive Borrelia burgdorferi antibody enzyme immunoassay and Western blot analysis (9 of 10 reactive immunoglobulin G bands and 1 of 3 immunoglobulin M bands) confirmed the diagnosis. Treatment with oral antibiotics and topical corticosteroids were necessary for resolution. Conclusions: Lyme disease may present as a unilateral posterior stromal keratitis, even in a pediatric population. Treatment requires both systemic and topical therapy.